THAP5 is a human cardiac-specific inhibitor of cell cycle that is cleaved by the proapoptotic Omi/HtrA2 protease during cell death
| العنوان: | THAP5 is a human cardiac-specific inhibitor of cell cycle that is cleaved by the proapoptotic Omi/HtrA2 protease during cell death |
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| 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 |
| بيانات النشر: | American Physiological Society, 2009. |
| سنة النشر: | 2009 |
| 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. |
| تدمد: | 1522-1539 0363-6135 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1d61a46748e20b97c8c94706f42a1163Test https://doi.org/10.1152/ajpheart.00234.2009Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1d61a46748e20b97c8c94706f42a1163 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221539 03636135 |
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