Changes in FADD levels, distribution, and phosphorylation in TNFα-induced apoptosis in hepatocytes is caspase-3, caspase-8 and BID dependent
| العنوان: | Changes in FADD levels, distribution, and phosphorylation in TNFα-induced apoptosis in hepatocytes is caspase-3, caspase-8 and BID dependent |
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| المؤلفون: | Xiao Min Yin, Richard A. Shapiro, Patricia Loughran, Timothy R. Billiar, Raghuveer Vallabhaneni, Youzhong Yuan, Xiaoying Zhang |
| المصدر: | Apoptosis |
| بيانات النشر: | Springer Science and Business Media LLC, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Male, Cytoplasm, Death Domain Receptor Signaling Adaptor Proteins, Cancer Research, Fas-Associated Death Domain Protein, Clinical Biochemistry, Active Transport, Cell Nucleus, Pharmaceutical Science, Apoptosis, Caspase 3, Biology, urologic and male genital diseases, Caspase 8, Article, Mice, Animals, Humans, FADD, Phosphorylation, Death domain, Membrane Potential, Mitochondrial, Mice, Knockout, Pharmacology, Tumor Necrosis Factor-alpha, Biochemistry (medical), Signal transducing adaptor protein, Cell Biology, Up-Regulation, Cell biology, Mice, Inbred C57BL, Caspases, Death-inducing signaling complex, Dactinomycin, Hepatocytes, biology.protein, biological phenomena, cell phenomena, and immunity, Signal transduction, BH3 Interacting Domain Death Agonist Protein, Signal Transduction |
| الوصف: | FADD/MORT1 (The adaptor protein of Fas Associate Death Domain/Mediator of Receptor Induced Toxicity) is essential for signal transduction of death receptor signaling. We have previously shown that FADD is significantly up-regulated in TNFalpha/ActD induced apoptosis. Over-expression of FADD also induces death of lung cancer cells and primary hepatocytes. We hypothesize that the increase in detectable FADD levels require the proximal steps in apoptotic signaling and speculated that FADD would be redistributed in cells destined to undergo apoptosis. We show that monomeric non-phosphorylated FADD is up-regulated in hepatocytes treated with TNFalpha/ActD and that it accumulates in the cytoplasm. Nuclear phosphorylated FADD decreases with TNFalpha/ActD treatment. Dimeric FADD in the cytoplasm remains constant with TNFalpha/ActD. The change in FADD levels and distribution was dependent on caspase-3, caspase-8 activity and the presence of BID. Thus, changes in FADD levels and distribution are downstream of caspase activation and mitochondria changes that are initiated by the formation of the DISC complex. Changes in FADD levels and distribution may represent a novel feed-forward mechanism to propagate apoptosis signaling in hepatocytes. |
| تدمد: | 1573-675X 1360-8185 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::860536e2108f2227c2cd6efd65151b09Test https://doi.org/10.1007/s10495-008-0228-3Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....860536e2108f2227c2cd6efd65151b09 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1573675X 13608185 |
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