المؤلفون: Lucia Cilenti, Meenakshi P. Balakrishnan, Martin Sterlicchi, Antonis S. Zervos, Federica del Monte, Camilla T. Ambivero, Xiao-Liang Wang, Xin L. Ma

المصدر: Journal of Molecular and Cellular Cardiology. 50:652-661

مصطلحات موضوعية: Scaffold protein, Programmed cell death, Blotting, Western, Myocardial Infarction, Apoptosis, Myocardial Reperfusion Injury, Coronary Artery Disease, DNA-binding protein, Article, Cell Line, Rats, Sprague-Dawley, Mice, Nuclear Matrix-Associated Proteins, Ubiquitin, Two-Hybrid System Techniques, medicine, Animals, Humans, Myocardial infarction, Nuclear protein, Molecular Biology, Cells, Cultured, Zinc finger transcription factor, biology, business.industry, Nuclear Proteins, Hydrogen Peroxide, Blotting, Northern, medicine.disease, Molecular biology, Rats, Cell biology, DNA-Binding Proteins, Mice, Inbred C57BL, Animals, Newborn, biology.protein, Cardiology and Cardiovascular Medicine, business, HeLa Cells, Protein Binding

الوصف: Abro1 (also known as KIAA0157) is a scaffold protein that recruits polypeptides to assemble the BRISC (BRCC36-containing isopeptidase complex) deubiquitinating (DUB) enzyme. The four subunits of BRISC enzyme include Abro1, NBA1, BRE, and BRCC36 proteins. The DUB activity of the BRISC enzyme is exclusively directed against Lys63-linked polyubiquitin that does not have a proteolytic role but regulates protein function. In this report, we identified Abro1 as a specific interactor of THAP5, a zinc finger transcription factor that is involved in G2/M control and apoptosis. Abro1 was predominantly expressed in the heart and its protein level was regulated following experimentally induced myocardial ischemia/reperfusion (MI/R) injury. Furthermore, in patients with coronary artery disease (CAD), there was a dramatic increase in Abro1 protein level in the myocardial infarction (MI) area. Increase in Abro1 leads to a significant reduction in Lys63-linked ubiquitination of specific protein targets. Reducing the Abro1 protein level exacerbated cellular damage and cell death of cardiomyocytes due to MI/R injury. Additionally, overexpression of Abro1 in a heterologous system provided significant protection against oxidative stress-induced apoptosis. In conclusion, our results demonstrate that Abro1 protein level substantially increases in myocardial injury and coronary artery disease and this up-regulation is part of a novel cardioprotective mechanism. In addition, our data suggest a potential new link between Lys63-specific ubiquitination, its modulation by the BRISC DUB enzyme, and the development and progression of heart disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2ce93002b161171581610efcd0620ba1Test
https://doi.org/10.1016/j.yjmcc.2010.12.015Test

المؤلفون: Xiaoman Shawn Li, Lucia Cilenti, James Turkson, Yamafumi Goto, Camilla T. Ambivero, Meenakshi P. Balakrishnan, Minoru Takata, Antonis S. Zervos

المصدر: Biochemical and Biophysical Research Communications. 404:195-200

مصطلحات موضوعية: Programmed cell death, Skin Neoplasms, Transcription, Genetic, DNA damage, Biophysics, Repressor, Antineoplastic Agents, Apoptosis, Biology, Biochemistry, DNA-binding protein, Article, Mice, Genes, Reporter, Cell Line, Tumor, Animals, Humans, Nuclear protein, Melanoma, Molecular Biology, Zinc finger, Reporter gene, Nuclear Proteins, Cell Biology, Molecular biology, Rats, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Repressor Proteins, Cisplatin, DNA Damage

الوصف: THAP5 was originally isolated as a specific interactor and substrate of the mitochondrial pro-apoptotic Omi/HtrA2 protease. It is a human zinc finger protein characterized by a restricted pattern of expression and the lack of orthologs in mouse and rat. The biological function of THAP5 is unknown but our previous studies suggest it could regulate G2/M transition in kidney cells and could be involved in human cardiomyocyte cell death associated with coronary artery disease (CAD). In this report, we expanded our studies on the properties and function of THAP5 in human melanoma cells. THAP5 was expressed in primary human melanocytes as well as in all melanoma cell lines that were tested. THAP5 protein level was significantly induced by UV irradiation or cisplatin treatment, conditions known to cause DNA damage. The induction of THAP5 correlated with a significant increase in apoptotic cell death. In addition, we show that THAP5 is a nuclear protein that could recognize and bind a specific DNA motif. THAP5 could also repress the transcription of a reporter gene in a heterologous system. Our work suggests that THAP5 is a DNA-binding protein and a transcriptional repressor. Furthermore, THAP5 has a pro-apoptotic function and it was induced in melanoma cells under conditions that promoted cell death.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fae2c6c7617ac44769ee8f6577a2e571Test
https://doi.org/10.1016/j.bbrc.2010.11.092Test

المؤلفون: Zineb Mashak, Emad S. Alnemri, Paiyal Popat, Antonis S. Zervos, Lucia Cilenti, Meenakshi P. Balakrishnan

المصدر: American Journal of Physiology-Heart and Circulatory Physiology. 297:H643-H653

مصطلحات موضوعية: Programmed cell death, Physiology, medicine.medical_treatment, Myocardial Infarction, Antineoplastic Agents, Apoptosis, Coronary Artery Disease, Pyrimidinones, Biology, Mitochondrion, Kidney, Transfection, Gene Expression Regulation, Enzymologic, Mitochondria, Heart, Substrate Specificity, Mitochondrial Proteins, Two-Hybrid System Techniques, Yeasts, Physiology (medical), medicine, Homeostasis, Humans, RNA, Messenger, Nuclear protein, Cell Nucleus, Serine protease, Protease, Myocardium, Cell Cycle, Serine Endopeptidases, Nuclear Proteins, Thiones, Articles, Hydrogen Peroxide, High-Temperature Requirement A Serine Peptidase 2, Cell cycle, Oxidants, Cell biology, DNA-Binding Proteins, Biochemistry, Cytoplasm, biology.protein, Cisplatin, Cardiology and Cardiovascular Medicine, HeLa Cells

الوصف: Omi/HtrA2 is a mitochondrial serine protease that has a dual function: while confined in the mitochondria, it promotes cell survival, but when released into the cytoplasm, it participates in caspase-dependent as well as caspase-independent cell death. To investigate the mechanism of Omi/HtrA2's function, we set out to isolate and characterize novel substrates for this protease. We have identified Thanatos-associated protein 5 (THAP5) as a specific interactor and substrate of Omi/HtrA2 in cells undergoing apoptosis. This protein is an uncharacterized member of the THAP family of proteins. THAP5 has a unique pattern of expression and is found predominantly in the human heart, although a very low expression is also seen in the human brain and muscle. THAP5 protein is localized in the nucleus and, when ectopically expressed, induces cell cycle arrest. During apoptosis, THAP5 protein is degraded, and this process can be blocked using a specific Omi/HtrA2 inhibitor, leading to reduced cell death. In patients with coronary artery disease, THAP5 protein levels substantially decrease in the myocardial infarction area, suggesting a potential role of this protein in human heart disease. This work identifies human THAP5 as a cardiac-specific nuclear protein that controls cell cycle progression. Furthermore, during apoptosis, THAP5 is cleaved and removed by the proapoptotic Omi/HtrA2 protease. Taken together, we provide evidence to support that THAP5 and its regulation by Omi/HtrA2 provide a new link between cell cycle control and apoptosis in cardiomyocytes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1d61a46748e20b97c8c94706f42a1163Test
https://doi.org/10.1152/ajpheart.00234.2009Test

المؤلفون: Carlo Fusco, Antonis S. Zervos, Alexandre Reymond

المصدر: Genomics. 51(3)

مصطلحات موضوعية: Leucine zipper, Molecular Sequence Data, Nuclear Localization Signals, Molecular cloning, Retinoblastoma Protein, Cell Line, Complementary DNA, Genetics, Humans, Amino Acid Sequence, RNA, Messenger, Cloning, Molecular, Gene, In Situ Hybridization, Fluorescence, Leucine Zippers, Endodeoxyribonucleases, biology, Base Sequence, Binding protein, Nucleic acid sequence, Retinoblastoma protein, Chromosome Mapping, Nuclear Proteins, Sequence Analysis, DNA, Phosphoproteins, Molecular biology, DNA-Binding Proteins, Alcohol Oxidoreductases, biology.protein, Adenovirus E1A Proteins, Carrier Proteins, Chromosomes, Human, Pair 18, Nuclear localization sequence

الوصف: We describe the isolation and characterization of a novel cDNA encoding a polypeptide that interacts in a yeast two-hybrid system as well as in mammalian cells with the retinoblastoma (RB) protein. This new protein, which we call Rim, consists of 897 amino acids, has two leucine zipper motifs, and has a LECEE sequence previously identified as an RB-binding domain. Rim also has an E1A/CtBP-binding motif and four putative nuclear localization signals. Rim mRNA is expressed ubiquitously at low levels in all human adult tissues tested and at much higher levels in several tumor cell lines. The Rim gene (HGMW-approved symbol RBBP8) is localized on human chromosome 18q11.2.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f9c7d4cefd7dae4a9e8c9e08460bc047Test
https://pubmed.ncbi.nlm.nih.gov/9721205Test