@article{%a1.%Yb_90,

title = {Alternative Splicing, RNA Editing, and the Current Limits of Next Generation Sequencing},

author = {Piazzi M and Bavelloni A and Salucci S and Faenza I and Blalock WL},

url = {https://www.mdpi.com/2073-4425/14/7/1386},

doi = {10.3390/genes14071386},

year  = {2023},

date = {2023-08-07},

journal = {Genes},

volume = {14},

issue = {7},

pages = {1386},

abstract = {The advent of next generation sequencing (NGS) has fostered a shift in basic analytic strategies of a gene expression analysis in diverse pathologies for the purposes of research, pharmacology, and personalized medicine. What was once highly focused research on individual signaling pathways or pathway members has, from the time of gene expression arrays, become a global analysis of gene expression that has aided in identifying novel pathway interactions, the discovery of new therapeutic targets, and the establishment of disease-associated profiles for assessing progression, stratification, or a therapeutic response. But there are significant caveats to this analysis that do not allow for the construction of the full picture. The lack of timely updates to publicly available databases and the "hit and miss" deposition of scientific data to these databases relegate a large amount of potentially important data to "garbage", begging the question, "how much are we really missing?" This brief perspective aims to highlight some of the limitations that RNA binding/modifying proteins and RNA processing impose on our current usage of NGS technologies as relating to cancer and how not fully appreciating the limitations of current NGS technology may negatively affect therapeutic strategies in the long run.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Y_132,

title = {Mineralocorticoid Receptor Antagonism Prevents Type 2 Familial Partial Lipodystrophy Brown Adipocyte Dysfunction},

author = {Schena E and Mattioli E and Peres C and Zanotti L and Morselli P and Iozzo P and Guzzardi MA and Bernardini C and Forni M and Nesci S and Caprio M and Cecchetti C and Pagotto U and Gabusi E and Cattini L and Lisignoli G and Blalock WL and Gambineri A and Lattanzi G},

url = {https://www.mdpi.com/2073-4409/12/22/2586},

doi = {10.3390/cells12222586},

year  = {2023},

date = {2023-10-10},

urldate = {2023-10-10},

journal = {CELLS},

volume = {12},

issue = {22},

pages = {2586},

abstract = {Type-2 Familial Partial Lipodystrophy (FPLD2), a rare lipodystrophy caused by LMNA mutations, is characterized by a loss of subcutaneous fat from the trunk and limbs and excess accumulation of adipose tissue in the neck and face. Several studies have reported that the mineralocorticoid receptor (MR) plays an essential role in adipose tissue differentiation and functionality. We previously showed that brown preadipocytes isolated from a FPLD2 patient's neck aberrantly differentiate towards the white lineage. As this condition may be related to MR activation, we suspected altered MR dynamics in FPLD2. Despite cytoplasmic MR localization in control brown adipocytes, retention of MR was observed in FPLD2 brown adipocyte nuclei. Moreover, overexpression of wild-type or mutated prelamin A caused GFP-MR recruitment to the nuclear envelope in HEK293 cells, while drug-induced prelamin A co-localized with endogenous MR in human preadipocytes. Based on in silico analysis and in situ protein ligation assays, we could suggest an interaction between prelamin A and MR, which appears to be inhibited by mineralocorticoid receptor antagonism. Importantly, the MR antagonist spironolactone redirected FPLD2 preadipocyte differentiation towards the brown lineage, avoiding the formation of enlarged and dysmorphic lipid droplets. Finally, beneficial effects on brown adipose tissue activity were observed in an FPLD2 patient undergoing spironolactone treatment. These findings identify MR as a new lamin A interactor and a new player in lamin A-linked lipodystrophies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_107,

title = {Phospholipase Family Enzymes in Lung Cancer: Looking for Novel Therapeutic Approaches},

author = {Salucci S and Aramini B and Bartoletti-Stella A and Versari I and Martinelli G and Blalock WL and Stella F and Faenza I},

url = {https://www.mdpi.com/2072-6694/15/12/3245},

doi = {10.3390/cancers15123245},

year  = {2023},

date = {2023-08-08},

journal = {Cancers-Basel},

volume = {15},

issue = {12},

pages = {3245},

abstract = {Lung cancer (LC) is the second most common neoplasm in men and the third most common in women. In the last decade, LC therapies have undergone significant improvements with the advent of immunotherapy. However, the effectiveness of the available treatments remains insufficient due to the presence of therapy-resistant cancer cells. For decades, chemotherapy and radiotherapy have dominated the treatment strategy for LC; however, relapses occur rapidly and result in poor survival. Malignant lung tumors are classified as either small- or non-small-cell lung carcinoma (SCLC and NSCLC). Despite improvements in the treatment of LC in recent decades, the benefits of surgery, radiotherapy, and chemotherapy are limited, although they have improved the prognosis of LC despite the persistent low survival rate due to distant metastasis in the late stage. The identification of novel prognostic molecular markers is crucial to understand the underlying mechanisms of LC initiation and progression. The potential role of phosphatidylinositol in tumor growth and the metastatic process has recently been suggested by some researchers. Phosphatidylinositols are lipid molecules and key players in the inositol signaling pathway that have a pivotal role in cell cycle regulation, proliferation, differentiation, membrane trafficking, and gene expression. In this review, we discuss the current understanding of phosphoinositide-specific phospholipase enzymes and their emerging roles in LC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_34,

title = {Combined Treatment with PI3K Inhibitors BYL-719 and CAL-101 Is a Promising Antiproliferative Strategy in Human Rhabdomyosarcoma Cells},

author = {Piazzi M and Bavelloni A and Cenni V and Salucci S and Bartoletti Stella A and Tomassini E and Scotlandi K and Blalock WL and Faenza I},

url = {https://www.mdpi.com/1420-3049/27/9/2742},

doi = {10.3390/molecules27092742},

year  = {2022},

date = {2022-08-18},

journal = {Molecules},

volume = {27},

issue = {9},

pages = {2742},

abstract = {Rhabdomyosarcoma (RMS) is a highly malignant and metastatic pediatric cancer arising from skeletal muscle myogenic progenitors. Recent studies have shown an important role for AKT signaling in RMS progression. Aberrant activation of the PI3K/AKT axis is one of the most frequent events occurring in human cancers and serves to disconnect the control of cell growth, survival, and metabolism from exogenous growth stimuli. In the study reported here, a panel of five compounds targeting the catalytic subunits of the four class I PI3K isoforms (p110α, BYL-719 inhibitor; p110β, TGX-221 inhibitor; p110γ, CZC24832; p110δ, CAL-101 inhibitor) and the dual p110α/p110δ, AZD8835 inhibitor, were tested on the RMS cell lines RD, A204, and SJCRH30. Cytotoxicity, cell cycle, apoptosis, and the activation of downstream targets were analyzed. Of the individual inhibitors, BYL-719 demonstrated the most anti-tumorgenic properties. BYL-719 treatment resulted in G1/G0 phase cell cycle arrest and apoptosis. When combined with CAL-101, BYL-719 decreased cell viability and induced apoptosis in a synergistic manner, equaling or surpassing results achieved with AZD8835. In conclusion, our findings indicate that BYL-719, either alone or in combination with the p110δ inhibitor, CAL-101, could represent an efficient treatment for human rhabdomyosarcoma presenting with aberrant upregulation of the PI3K signaling pathway.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Yb_63,

title = {Extra Virgin Olive Oil (EVOO), a Mediterranean Diet Component, in the Management of Muscle Mass and Function Preservation},

author = {Salucci S and Bartoletti-Stella A and Bavelloni A and Aramini B and Blalock WL and Fabbri F and Vannini I and Sambri V and Stella F and Faenza I},

url = {https://www.mdpi.com/2072-6643/14/17/3567},

doi = {10.3390/nu14173567},

year  = {2022},

date = {2022-03-31},

journal = {Nutrients},

volume = {14},

issue = {17},

pages = {3567},

abstract = {Aging results in a progressive decline in skeletal muscle mass, strength and function, a condition known as sarcopenia. This pathological condition is due to multifactorial processes including physical inactivity, inflammation, oxidative stress, hormonal changes, and nutritional intake. Physical therapy remains the standard approach to treat sarcopenia, although some interventions based on dietary supplementation are in clinical development. In this context, thanks to its known anti-inflammatory and antioxidative properties, there is great interest in using extra virgin olive oil (EVOO) supplementation to promote muscle mass and health in sarcopenic patients. To date, the molecular mechanisms responsible for the pathological changes associated with sarcopenia remain undefined; however, a complete understanding of the signaling pathways that regulate skeletal muscle protein synthesis and their behavior during sarcopenia appears vital for defining how EVOO might attenuate muscle wasting during aging. This review highlights the main molecular players that control skeletal muscle mass, with particular regard to sarcopenia, and discusses, based on the more recent findings, the potential of EVOO in delaying/preventing loss of muscle mass and function, with the aim of stimulating further research to assess dietary supplementation with EVOO as an approach to prevent or delay sarcopenia in aging individuals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1.%Ybw,

title = {Novel Targeting of DNA Methyltransferase Activity Inhibits Ewing Sarcoma Cell Proliferation and Enhances Tumor Cell Sensitivity to DNA Damaging Drugs by Activating the DNA Damage Response},

author = {Cristalli C and Manara MC and Valente S and Pellegrini E and Bavelloni A and De Feo A and Blalock WL and Di Bello E and Pineyro D and Merkel A and Esteller M and Tirado OM and Mai A and Scotlandi K},

url = {https://www.frontiersin.org/articles/10.3389/fendo.2022.876602/full},

doi = {10.3389/fendo.2022.876602},

year  = {2022},

date = {2022-08-30},

urldate = {2022-08-30},

journal = {Frontiers in endocrinology},

volume = {13},

pages = {876602},

abstract = {DNA methylation is an important component of the epigenetic machinery that regulates the malignancy of Ewing sarcoma (EWS), the second most common primary bone tumor in children and adolescents. Coordination of DNA methylation and DNA replication is critical for maintaining epigenetic programming and the DNMT1 enzyme has been demonstrated to have an important role in both maintaining the epigenome and controlling cell cycle. Here, we showed that the novel nonnucleoside DNMT inhibitor (DNMTi) MC3343 induces a specific depletion of DNMT1 and affects EWS tumor proliferation through a mechanism that is independent on DNA methylation. Depletion of DNMT1 causes perturbation of the cell cycle, with an accumulation of cells in the G1 phase, and DNA damage, as revealed by the induction of γH2AX foci. These effects elicited activation of p53-dependent signaling and apoptosis in p53wt cells, while in p53 mutated cells, persistent micronuclei and increased DNA instability was observed. Treatment with MC3343 potentiates the efficacy of DNA damaging agents such as doxorubicin and PARP-inhibitors (PARPi). This effect correlates with increased DNA damage and synergistic tumor cytotoxicity, supporting the use of the DNMTi MC3343 as an adjuvant agent in treating EWS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y__500,

title = {Ectopic Expression of Ankrd2 Affects Proliferation, Motility and Clonogenic Potential of Human Osteosarcoma Cells. },

author = {Piazzi M and Kojic S and Capanni C and Stamenkovic N and Bavelloni A and Marin O and Lattanzi G and Blalock WL and Cenni V},

url = {https://www.mdpi.com/2072-6694/13/2/174},

doi = {10.3390/cancers13020174},

year  = {2021},

date = {2021-03-09},

urldate = {2021-03-09},

journal = {Cancers (Basel)},

volume = {13},

number = {2},

pages = {e174},

abstract = {Ankrd2 is a protein known for being mainly expressed in muscle fibers, where it participates in the mechanical stress response. Since both myocytes and osteoblasts are mesenchymal-derived cells, we were interested in examining the role of Ankrd2 in the progression of osteosarcoma which features a mechano-stress component. Although having been identified in many tumor-derived cell lines and -tissues, no study has yet described nor hypothesized any involvement for this protein in osteosarcoma tumorigenesis. In this paper, we report that Ankrd2 is expressed in cell lines obtained from human osteosarcoma and demonstrate a contribution by this protein in the pathogenesis of this insidious disease. Ankrd2 involvement in osteosarcoma development was evaluated in clones of Saos2, U2OS, HOS and MG63 cells stably expressing Ankrd2, through the investigation of hallmark processes of cancer cells. Interestingly, we found that exogenous expression of Ankrd2 influenced cellular growth, migration and clonogenicity in a cell line-dependent manner, whereas it was able to improve the formation of 3D spheroids in three out of four cellular models and enhanced matrix metalloproteinase (MMP) activity in all tested cell lines. Conversely, downregulation of Ankrd2 expression remarkably reduced proliferation and clonogenic potential of parental cells. As a whole, our data present Ankrd2 as a novel player in osteosarcoma development, opening up new therapeutic perspectives.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Yb,

title = {Opposing forces fight over the same ground to regulate interferon signaling.},

author = {Blalock WL},

url = {https://portlandpress.com/biochemj/article/478/10/1853/228676/Opposing-forces-fight-over-the-same-ground-to},

doi = {10.1042/BCJ20210110},

year  = {2021},

date = {2021-05-17},

journal = {Biochemical journal},

volume = {478},

number = {10},

pages = {1853-1859},

abstract = {The current SARS-CoV-2 pandemic has spurred new interest in interferon signaling in response to viral pathogens. Much of what we know about the signaling molecules and associated signal transduction induced during the host cellular response to viral pathogens has been gained from research conducted from the 1990's to the present day, but certain intricacies of the mechanisms involved, still remain unclear. In a recent study by Vaughn et al. the authors examine one of the main mechanisms regulating interferon induction following viral infection, the RIG-I/MAVS/IRF3 pathway, and find that similar to PKR both DICER interacting proteins, PACT and TRBP, regulate RIG-I signaling in an opposing manner. More specifically, the reported findings demonstrate, like others, that PACT stimulates RIG-I-mediated signaling in a manner independent of PACT dsRNA-binding ability or phosphorylation at sites known to be important for PACT-dependent PKR activation. In contrast, they show for the first time that TRBP inhibits RIG-I-mediated signaling. RIG-I inhibition by TRBP did not require phosphorylation of sites shown to be important for inhibiting PKR, nor did it involve PACT or PKR, but it did require the dsRNA-binding ability of TRBP. These findings open the door to a complex co-regulation of RIG-I, PKR, MDA5, miRNA processing, and interferon induction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Yb_61,

title = {Revisiting the Role of GSK3, A Modulator of Innate Immunity, in Idiopathic Inclusion Body Myositis.},

author = {Piazzi M and Bavelloni A and Cenni V and Faenza I and Blalock WL},

url = {https://www.mdpi.com/2073-4409/10/11/3255},

doi = {10.3390/cells10113255},

year  = {2021},

date = {2021-12-06},

journal = {Cells},

volume = {10},

number = {11},

pages = {3255},

abstract = {Idiopathic or sporadic inclusion body myositis (IBM) is the leading age-related (onset >50 years of age) autoimmune muscular pathology, resulting in significant debilitation in affected individuals. Once viewed as primarily a degenerative disorder, it is now evident that much like several other neuro-muscular degenerative disorders, IBM has a major autoinflammatory component resulting in chronic inflammation-induced muscle destruction. Thus, IBM is now considered primarily an inflammatory pathology. To date, there is no effective treatment for sporadic inclusion body myositis, and little is understood about the pathology at the molecular level, which would offer the best hopes of at least slowing down the degenerative process. Among the previously examined potential molecular players in IBM is glycogen synthase kinase (GSK)-3, whose role in promoting TAU phosphorylation and inclusion bodies in Alzheimer's disease is well known. This review looks to re-examine the role of GSK3 in IBM, not strictly as a promoter of TAU and Abeta inclusions, but as a novel player in the innate immune system, discussing some of the recent roles discovered for this well-studied kinase in inflammatory-mediated pathology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_96,

title = {AKT-Dependent Phosphorylation of ADAR1p110 and ADAR2 Represents a New and Important Link Between Cell Signaling and RNA Editing.},

author = {Piazzi M and Bavelloni A and Gallo A and Blalock WL},

url = {https://www.liebertpub.com/doi/abs/10.1089/dna.2020.5351?rfr_dat=cr_pub%3Dpubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&journalCode=dna},

doi = {10.1089/dna.2020.5351},

year  = {2020},

date = {2020-01-01},

journal = {DNA and cell biology},

volume = {39},

number = {3},

pages = {343-348},

abstract = {RNA editing is a process by which nascent RNA transcripts are covalently modified, thus enhancing the complexity of the transcriptome. The most common modifications are deaminations of adenosine to inosine at sites of complex RNA secondary structure, a process that is carried out by the adenosine deaminase acting on double-strand RNA (ADAR) family of RNA editases. Although much has been learned about the ADAR family members since their discovery, very little information on their post-transcriptional regulation has been reported. Similar to most proteins, the ADAR family members are post-translationally modified at multiple sites. We recently reported that members of the AKT kinase family directly phosphorylate ADAR1p110 and ADAR2 on a conserved threonine within the catalytic domain of the protein. Phosphorylation was observed to differentially inhibit the enzymatic activity of the ADAR proteins toward known RNA substrates. The direct downstream involvement of the AKT kinases in multiple major signaling pathways associated with cell survival, growth, glucose metabolism (insulin signaling), and differentiation is well established; thus, the AKT kinases represent a link between ADAR-dependent A-to-I editing and major signal transduction pathways that are necessary for cell maintenance and development.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_422,

title = {Cancer therapy and treatments during COVID-19 era},

author = {Akula SM and Abrams SL and Steelman LS and Candido S and Libra M and Lerpiriyapong K and Cocco L and Ramazzotti G and Ratti S and Follo MY and Martelli AM and Blalock WL and Piazzi M and Montalto G and Cervello M and Notarbartolo M and Basecke J and McCubrey JA},

url = {https://www.sciencedirect.com/science/article/pii/S2212492620300506?via%3Dihub},

doi = {10.1016/j.jbior.2020.100739},

year  = {2020},

date = {2020-01-01},

journal = {Advances in Biological Regulation},

volume = {77},

pages = {100739},

abstract = {The COVID-19 pandemic has put a serious strain on health treatments as well at the economies of many nations. Unfortunately, there is not currently available vaccine for SARS-Cov-2/COVID-19. Various types of patients have delayed treatment or even routine check-ups and we are adapting to a virtual world. In many cases, surgeries are delayed unless they are essential. This is also true with regards to cancer treatments and screening. Interestingly, some existing drugs and nutraceuticals have been screened for their effects on COVID-19. Certain FDA approved drugs, vitamin, natural products and trace minerals may be repurposed to treat or improve the prevention of COVID-19 infections and disease progression. This review article will summarize how the treatments of various cancer patients has changed during the COVID-19 era as well as discuss the promise of some existing drugs and other agents to be repurposed to treat this disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_467,

title = {Expression of the double-stranded RNA-dependent kinase PKR influences osteosarcoma attachment independent growth, migration, and invasion.},

author = {Piazzi M and Bavelloni A and Greco S and Focaccia E and Orsini A and Benini S and Gambarotti M and Faenza I and Blalock WL},

url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.29024},

doi = {10.1002/jcp.29024},

year  = {2020},

date = {2020-01-01},

journal = {Journal of cellular physiology},

volume = {235},

number = {2},

pages = {1103-1119},

abstract = {Osteosarcoma (OS) is a rare, insidious tumor of mesenchymal origin that most often affects children, adolescents, and young adults. While the primary tumor can be controlled with chemotherapy and surgery, it is the lung metastases that are eventually fatal. Multiple studies into the initial drivers of OS development have been undertaken, but few of these have examined innate immune/inflammatory signaling. A central figure in inflammatory signaling is the innate immune/stress-activated kinase double-stranded RNA-dependent protein kinase (PKR). To characterize the role of PKR in OS, U2OS, and SaOS-2 osteosarcoma cell lines were stably transfected with wild-type or dominant-negative (DN) PKR. Overexpression of PKR enhanced colony formation in soft agar (U2OS and SaOS-2), enhanced cellular migration (U2OS), and invasive migration (SaOS-2). In contrast, overexpression of DN-PKR inhibited attachment-independent growth, migration and/or invasion. These data demonstrate a role for inflammatory signaling in OS formation and migration/invasion and suggest the status of PKR expression/activation may have prognostic value.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_97,

title = {Expression of the double-stranded RNA-dependent kinase PKR influences osteosarcoma attachment independent growth, migration, and invasion.},

author = {Piazzi M and Bavelloni A and Greco S and Focaccia E and Orsini A and Benini S and Gambarotti M and Faenza I and Blalock WL},

url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.29024},

doi = {10.1002/jcp.29024},

year  = {2020},

date = {2020-02-27},

journal = {Journal of cellular physiology},

volume = {235},

number = {2},

pages = {1103-1119},

abstract = {Osteosarcoma (OS) is a rare, insidious tumor of mesenchymal origin that most often affects children, adolescents, and young adults. While the primary tumor can be controlled with chemotherapy and surgery, it is the lung metastases that are eventually fatal. Multiple studies into the initial drivers of OS development have been undertaken, but few of these have examined innate immune/inflammatory signaling. A central figure in inflammatory signaling is the innate immune/stress-activated kinase double-stranded RNA-dependent protein kinase (PKR). To characterize the role of PKR in OS, U2OS, and SaOS-2 osteosarcoma cell lines were stably transfected with wild-type or dominant-negative (DN) PKR. Overexpression of PKR enhanced colony formation in soft agar (U2OS and SaOS-2), enhanced cellular migration (U2OS), and invasive migration (SaOS-2). In contrast, overexpression of DN-PKR inhibited attachment-independent growth, migration and/or invasion. These data demonstrate a role for inflammatory signaling in OS formation and migration/invasion and suggest the status of PKR expression/activation may have prognostic value.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_466,

title = {Glycogen synthase kinase (GSK)-3 and the double-strand RNA-dependent kinase, PKR: When two kinases for the common good turn bad},

author = {Piazzi M and Bavelloni A and Faenza I and Blalock WL},

url = {https://www.sciencedirect.com/science/article/pii/S0167488920301270?via%3Dihub},

doi = {10.1016/j.bbamcr.2020.118769},

year  = {2020},

date = {2020-01-01},

journal = {Biochimica et biophysica acta. Molecular cell research},

volume = {1867},

number = {10},

pages = {118769},

abstract = {Glycogen synthase kinase (GSK)-3α/β and the double-stranded RNA-dependent kinase PKR are two sentinel kinases that carry-out multiple similar yet distinct functions in both the cytosol and the nucleus. While these kinases belong to separate signal transduction cascades, they demonstrate an uncanny propensity to regulate many of the same proteins either through direct phosphorylation or by altering transcription/translation, including: c-MYC, NF-κB, p53 and TAU, as well as each another. A significant number of studies centered on the GSK3 kinases have led to the identification of the GSK3 interactome and a number of substrates, which link GSK3 activity to metabolic control, translation, RNA splicing, ribosome biogenesis, cellular division, DNA repair and stress/inflammatory signaling. Interestingly, many of these same pathways and processes are controlled by PKR, but unlike the GSK3 kinases, a clear picture of proteins interacting with PKR and a complete listing of its substrates is still missing. In this review, we take a detailed look at what is known about the PKR and GSK3 kinases, how these kinases interact to influence common cellular processes (innate immunity, alternative splicing, translation, glucose metabolism) and how aberrant activation of these kinases leads to diseases such as Alzheimer's disease (AD), diabetes mellitus (DM) and cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%i,

title = {AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity.},

author = {Bavelloni A and Focaccia E and Piazzi M and Raffini M and Cesarini V and Tomaselli S and Orsini A and Ratti S and Faenza I and Cocco L and Gallo A and Blalock WL},

url = {https://www.fasebj.org/doi/abs/10.1096/fj.201800490RR},

doi = {10.1096/fj.201800490RR},

year  = {2019},

date = {2019-02-14},

journal = {FASEB Journal},

volume = {33},

number = {8},

pages = {9044-9061},

abstract = {Murine thymoma viral oncogene homolog (AKT) kinases target both cytosolic and nuclear substrates for phosphorylation. Whereas the cytosolic substrates are known to be closely associated with the regulation of apoptosis and autophagy or metabolism and protein synthesis, the nuclear substrates are, for the most part, poorly understood. To better define the role of nuclear AKT, potential AKT substrates were isolated from the nuclear lysates of leukemic cell lines using a phosphorylated AKT substrate antibody and identified in tandem mass spectrometry. Among the proteins identified was adenosine deaminase acting on RNA (ADAR)1p110, the predominant nuclear isoform of the adenosine deaminase acting on double-stranded RNA. Coimmunoprecipitation studies and in vitro kinase assays revealed that AKT-1, -2, and -3 interact with both ADAR1p110 and ADAR2 and phosphorylate these RNA editases. Using site-directed mutagenesis of suspected AKT phosphorylation sites, AKT was found to primarily phosphorylate ADAR1p110 and ADAR2 on T738 and T553, respectively, and overexpression of the phosphomimic mutants ADAR1p110 (T738D) and ADAR2 (T553D) resulted in a 50-100% reduction in editase activity. Thus, activation of AKT has a direct and major impact on RNA editing.-Bavelloni, A., Focaccia, E., Piazzi, M., Raffini, M., Cesarini, V., Tomaselli, S., Orsini, A., Ratti, S., Faenza, I., Cocco, L., Gallo, A., Blalock, W. L. AKT-dependent phosphorylation of the adenosine deaminases ADAR-1 and -2 inhibits deaminase activity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_73,

title = {Signal Transduction in Ribosome Biogenesis: A Recipe to Avoid Disaster.},

author = {Piazzi M and Bavelloni A and Gallo A and Faenza I and Blalock WL},

url = {https://www.mdpi.com/1422-0067/20/11/2718},

doi = {10.3390/ijms20112718},

year  = {2019},

date = {2019-06-03},

journal = {International journal of molecular sciences},

volume = {20},

number = {11},

pages = {e2718},

abstract = {Energetically speaking, ribosome biogenesis is by far the most costly process of the cell and, therefore, must be highly regulated in order to avoid unnecessary energy expenditure. Not only must ribosomal RNA (rRNA) synthesis, ribosomal protein (RP) transcription, translation, and nuclear import, as well as ribosome assembly, be tightly controlled, these events must be coordinated with other cellular events, such as cell division and differentiation. In addition, ribosome biogenesis must respond rapidly to environmental cues mediated by internal and cell surface receptors, or stress (oxidative stress, DNA damage, amino acid depletion, etc.). This review examines some of the well-studied pathways known to control ribosome biogenesis (PI3K-AKT-mTOR, RB-p53, MYC) and how they may interact with some of the less well studied pathways (eIF2α kinase and RNA editing/splicing) in higher eukaryotes to regulate ribosome biogenesis, assembly, and protein translation in a dynamic manner.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y%h,

title = {Therapeutic potential of nvp-bkm120 in human osteosarcomas cells.},

author = {Bavelloni A and Focaccia E and Piazzi M and Orsini A and Ramazzotti G and Cocco L and Blalock WL and Faenza I.},

url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.27911},

doi = {10.1002/jcp.27911},

year  = {2019},

date = {2019-07-19},

journal = {Journal of cellular physiology},

volume = {234},

number = {7},

pages = {10907},

abstract = {Osteosarcoma (OS) is the most common pediatric malignant neoplasia of the skeletal system. It is characterized by a high degree of malignancy and a severe tendency to metastasize. In the past decade, many studies have provided evidence that the phosphoinositide 3-kinase (PI3K) signaling pathway is one of the most frequently altered pathways in human cancer, and has a critical role in driving tumor initiation and progression. Here, we have analyzed the therapeutic potential of the pan-PI3K inhibitor NVP-BKM120, which has recently entered clinical Phase II for treatment of PI3K-dependent cancers on three OS cell lines. We observed a concentration- and time-dependent decrease of Ser473 p-Akt as well as reduced levels of Thr37/46 p-4E-BP1, an indicator of the mammalian target of rapamycin complex 1 activity. All OS cell lines used in this study responded to BKM120 treatment with an arrest of cell proliferation, an increase in cell mortality, and an increase in caspase-3 activity. MG-63 cells were the most responsive cell line, demonstrating a significant increase in sub-G1 cells, and a rapid induction of cell death. Furthermore, we demonstrate that BKM120 is more effective when used in combination with other standard chemotherapeutic drugs. Combining BKM120 with vincristine demonstrated a more synergistic effect than BKM120 with doxorubicin in all the lines. Hence, we suggest that BKM120 may be a novel therapy for the treatment of OS presenting with anomalous upregulation of the PI3K signaling pathway.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_231,

title = {Cell Cycle Arrest and Apoptosis Induced by Kinamycin F in Human Osteosarcoma Cells.},

author = {Bavelloni A and Focaccia E and Piazzi M and Errani C and Blalock WL and Faenza I},

url = {http://ar.iiarjournals.org/content/37/8/4103.long},

year  = {2017},

date = {2017-03-07},

journal = {Anticancer Research},

volume = {37},

number = {8},

pages = {4103-4109},

abstract = {Background/Aim: Kinamycin F is a bacterial metabolite which contains an unusual and potentially reactive diazo group that is known for its ability to inhibit cell growth. In this study, the potential anti-tumor activity of kinamycin F was investigated in three human osteosarcoma cell lines, MG-63, U-2 OS and HOS as an antitumor agent with a potentially novel target. Materials and Methods: Proliferation and cell viability were measured in three human osteosarcoma cell lines by commercially available kits. We also evaluated the effects of the drug on cell cycle progression using the Muse™ Cell Analyzer. Caspase-3 activity was determined by a fluorometric EnzChek assay kit. Finally, following treatment with kinamycin F the protein levels of cyclin D3, cyclin A and cdK-2 were examined. Results: Kinamycin F induced a concentration-dependent cell death in all the three cell lines. Flow cytometry revealed that kinamycin F treatment at 1 μM concentration significantly increased the cell population in the G2/M-phase (60-65%). Kinamycin F activated caspase 3 in all the three cell lines, clearly demonstrating that the growth inhibitory effect of kinamycin F can be attributed to apoptosis induction. Finally, kinamycin F suppressed osteosarcoma cell proliferation affecting cyclin A and D3 expression. Conclusion: Understanding the mechanism by which kinamycin F exerts its ability to inhibit cell growth may be a step forward in the development of new therapeutic strategies for the treatment of OS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_232,

title = {MiRNA-210: A Current Overview.},

author = {Bavelloni A and Ramazzotti G and Poli A and Piazzi M and Focaccia E and Blalock WL and Faenza I},

url = {http://ar.iiarjournals.org/content/37/12/6511.long},

year  = {2017},

date = {2017-12-18},

urldate = {2017-12-18},

journal = {Anticancer Research},

volume = {37},

number = {12},

pages = {6511-6521},

abstract = {microRNAs (miRNAs) are a group of highly conserved small non-coding RNAs that were found to enhance mRNA degradation or inhibit post-transcriptional translation. Accumulating evidence indicates that miRNAs contribute to tumorigenesis and cancer metastasis. microRNA-210 has been largely studied in the past several years and has been identified as a major miRNA induced under hypoxia. A variety of miR-210 targets have been identified pointing to its role, not only in mitochondrial metabolism, but also in angiogenesis, the DNA damage response, cell proliferation, and apoptosis. Based on earlier research findings, this review aims to provide a current overview on the involvement of miRNA-210 in biological processes and diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_305,

title = {BMP-2 Induced Expression of PLCbeta1 That Is a Positive Regulator of Osteoblast Differentiation.},

author = {Ramazzotti G and Bavelloni A and Blalock WL and Piazzi M and Cocco L and Faenza I},

url = {http://onlinelibrary.wiley.com/doi/10.1002/jcp.25107/abstract;jsessionid=9619766386605F1FBD94DD07A67E9B42.f04t02},

year  = {2016},

date = {2016-03-07},

journal = {Journal of Cellular Physiology},

volume = {231},

number = {3},

pages = {623-629},

abstract = {"Bone morphogenetic protein 2 (BMP-2) is a critical growth factor that directs osteoblast differentiation and bone formation. Phosphoinositide-phospholipase Cbeta 1 (PLCbeta1) plays a crucial role in the initiation of the genetic program responsible for muscle differentiation. Differentiation of C2C12 mouse myoblasts in response to insulin stimulation is characterized by a marked increase in nuclear PLCbeta1. Here, the function of PLCbeta1 in the osteogenic differentiation was investigated. Briefly, in C2C12 cells treated with BMP-2 we assist to a remarkable increase in PLCbeta1 protein and mRNA expression. The data regarding the influence on differentiation demonstrated that PLCbeta1 promotes osteogenic differentiation by up-regulating alkaline phosphatase (ALP). Moreover, PLCbeta1 is present in the nuclear compartment of these cells and overexpression of a cytosolic-PLCbeta1mutant (cyt-PLCbeta1), which lacks a nuclear localization sequence, prevented the differentiation of C2C12 cells into osteocytes. Recent evidence indicates that miRNAs act as important post transcriptional regulators in a large number of processes, including osteoblast differentiation. Since miR-214 is a regulator of Osterix (Osx) which is an osteoblast-specific transcription factor that is needful for osteoblast differentiation and bone formation, we further investigated whether PLCbeta1 could be a potential target of miR-214 in the control of osteogenic differentiation by gain- and loss- of function experiment. The results indicated that inhibition of miR-214 in C2C12 cells significantly enhances the protein level of PLCbeta1 and promotes C2C12 BMP-2-induced osteogenesis by targeting PLCbeta1. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.



"},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_283,

title = {Intolerant contact lens wearers exhibit ocular surface impairment despite 3 months wear discontinuation.},

author = {Giannaccare G and Blalock WL and Fresina M and Vagge A and Versura P},

url = {http://link.springer.com/article/10.1007%2Fs00417-016-3400-4},

doi = {10.1007/s00417-016-3400-4},

year  = {2016},

date = {2016-03-09},

journal = {Graefe's Archive for Clinical and Experimental Ophthalmology },

volume = {254},

number = {9},

pages = {1825-1831},

abstract = {Purpose: To evaluate ocular surface (OS) parameters recovery in intolerant contact lens (CL) wearers after a period of discontinuation. Methods: This is a retrospective analysis of data from 87 intolerant CL wearers who had discontinued their use for an average period of 12 weeks because of associated discomfort and failure to successfully refit. Data were collected from clinical charts. Data from 50 matched healthy volunteers served as controls. Clinical tests included subjective discomfort symptoms questionnaire (Ocular Surface Disease Index, OSDI), Schirmer test, break-up time (BUT), corneal esthesiometry and corneo-conjunctival staining. Laboratory tests included scraping and imprint cytology. Tear protein analysis included dosage of total tear protein (TP), lysozyme-C (LYS-C), lactoferrin (LACTO), zinc-α2-glycoprotein (ZAG-2), IgA heavy chain bands (Ig-A), and serum albumin (ALB). Data were correlated to wear parameters. Results: All values were significantly worse in intolerant CL wearers group (p always <0.001). In particular, lower values compared to controls were found for BUT, corneal esthesiometry, goblet cell density, LYS-C, LACTO, ZAG-2, and TP. On the contrary, higher values compared to controls were found for OSDI, staining, imprint cytology, scraping cytology, ALB, IgA-heavy chain. The IgA/LYS-C ratio calculated as an index of the increased activity of the IgA-producing cell was found significantly higher in the intolerant group and in correlation with discomfort symptoms. Conclusions: Ocular surface parameters were altered in intolerant CL wearers, even after a prolonged discontinuation period. Our data suggest that OS recovery necessary to successfully refit lenses may need a discontinuation time longer than 3 months.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_392,

title = {PI-PLCbeta1b affects Akt activation, cyclin E expression, and caspase cleavage, promoting cell survival in pro-B-lymphoblastic cells exposed to oxidative stress.},

author = {Piazzi M and Blalock WL and Bavelloni A and Faenza I and Raffini M and Tagliavini F and Manzoli L and Cocco L},

url = {https://www.fasebj.org/doi/full/10.1096/fj.14-259051?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&},

doi = {10.1096/fj.14-259051},

year  = {2015},

date = {2015-04-30},

journal = {FASEB Journal},

volume = {29},

number = {4},

pages = {1383-1394},

abstract = {The phosphoinositide-dependent signal transduction pathway has been implicated in the control of a variety of biologic processes, such as the regulation of cellular metabolism and homeostasis, cell proliferation and differentiation, and apoptosis. One of the key players in the regulation of inositol lipid signaling is the phospholipase Cbeta1 (PI-PLCbeta1), that hydrolyzes phosphatidylinositol 4,5-bisphosphate [PtIns(4,5)P2], giving rise to the second messengers inositol triphosphate and diacylglicerol. PI-PLCbeta1 has been associated with the regulation of several cellular functions, some of which have not yet been fully understood. In particular, it has been reported that PI-PLCbeta1 protects murine fibroblasts from oxidative stress-induced cell death. The mediators of oxidative stress, reactive oxygen species (ROS), have been shown to regulate major epigenetic processes, causing the silencing of tumor suppressors and enhancing the proliferation of leukemic cells underoxidative stress. Investigation of the interplay between ROS, PI-PLCbeta1, and their signaling mediators in leukemia might therefore reveal innovative targets of pharmacological therapy in the treatment for leukemia. In this work, we demonstrate that in pro-B-lymphoblastic cells (Ba/F3), treated with H2O2, PI-PLCbeta1b conferred resistance to cell death, promoting cellcycle progression and cell proliferation and influencing the expression of cyclin A and E. Interestingly, we found that,expression of PI-PLCbeta1b affects the activity of caspase-3, caspase-7, and of several protein kinases induced by oxidativestress. In particular, PI-PLCbeta1b expression completely abolished the phosphorylation of Erk1/2 MAP kinases, down-regulated phosphatase and tensin homolog (PTEN), and up-regulated the phosphorylation of Akt, thereby sustaining cellular proliferation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_394,

title = {PLCβ1a and PLCβ1b selective regulation and cyclin D3 modulation reduced by kinamycin F during k562 cell differentiation.},

author = {Bavelloni A and Dmitrienko GI and Goodfellow VJ and Ghavami A and Piazzi M and Blalock WL and Chiarini F and Cocco L and Faenza I},

url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.24776},

doi = {10.1002/jcp.24776},

year  = {2015},

date = {2015-03-03},

journal = {Journal of Cellular Physiology},

volume = {230},

number = {3},

abstract = {Here we report that both PLCβ1a and PLCβ1b are relevant regulators of erythropoiesis in that kinamycin F, a potent inducer of γ-globin production in K562 cells, caused a selectively reduction of both PLCβ1 isozymes even though the results point out that the effect of the drug is mainly directed toward the expression of the PLCβ1a isoform. We have identified a different role for the two isozymes as regulators of K562 differentiation process induced by kinamycin F. The overexpression of PLCβ1b induced an increase in γ-globin expression even in the absence of kinamycin F. Moreover during K562 differentiation, cyclin D3 level is regulated by PLCβ1 signaling pathway. Namely the amplification of the expression of the PLCβ1a, but not of PLCβ1b, is able to maintain high levels of expression of cyclin D3 even after treatment with kinamycin F. This could be due to their different distribution in the cell compartments since the amount of PLCβ1b is mainly present in the nucleus in respect to PLCβ1a. Our data indicate that the amplification of PLCβ1a expression, following treatment with kinamycin F, confers a real advantage to K562 cells viability and protects cells themselves from apoptosis.2014 Wiley Periodicals, Inc., A Wiley Company.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{%a1:%Y_399,

title = {Prohibitin 2: At a communications crossroads.},

author = {Bavelloni A and Piazzi M and Raffini M and Faenza I and Blalock WL},

url = {https://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/iub.1366},

doi = {10.1002/iub.1366},

year  = {2015},

date = {2015-04-24},

journal = {IUBMB Life},

volume = {67},

number = {4},

pages = {239-254},

abstract = {Prohibitins (PHBs) are a highly conserved class of proteins first discovered as inhibitors of cellular proliferation. Since then PHBs have been found to have a significant role in transcription, nuclear signaling, mitochondrial structural integrity, cell division, and cellular membrane metabolism, placing these proteins among the key regulators of pathologies such as cancer, neuromuscular degeneration, and other metabolic diseases. The human genome encodes two PHB proteins, prohibitin 1 (PHB1) and prohibitin 2 (PHB2), which function not only as a heterodimeric complex, but also independently. While many previous reviews have focused on the better characterized prohibitin, PHB1, this review focuses on PHB2 and new data concerning its cellular functions both in complex with PHB1 and independent of PHB1. 2015 International Union of Biochemistry and Molecular Biology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}