PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis
- 4 August 1999
- journal article
- Published by Springer Nature in Oncogene
- Vol. 18 (31) , 4409-4415
- https://doi.org/10.1038/sj.onc.1202831
Abstract
PED/PEA-15 is a recently cloned 15 kDa protein possessing a death effector domain (DED). In MCF-7 and HeLa cells, a fivefold overexpression of PED/PEA-15 blocked FasL and TNFα apoptotic effects. This effect of PED overexpression was blocked by inhibition of PKC activity. In MCF-7 and HeLa cell lysates, PED/PEA-15 co-precipitated with both FADD and FLICE. PED/PEA-15-FLICE association was inhibited by overexpression of the wild-type but not of a DED-deletion mutant of FADD. Simultaneous overexpression of PED/PEA-15 with FADD and FLICE inhibited FADD-FLICE co-precipitation by threefold. Based on cleavage of the FLICE substrate PARP, this inhibitory effect was paralleled by a threefold decline in FLICE activation in response to TNF-α. TNFα, in turn, reduces PED association with the endogenous FADD and FLICE of the cells. Thus, PED/PEA-15 is an endogenous protein inhibiting FAS and TNFR1-mediated apoptosis. At least in part, this function may involve displacement of FADD-FLICE binding through the death effector domain of PED/PEA-15.Keywords
This publication has 23 references indexed in Scilit:
- PED/PEA-15 gene controls glucose transport and is overexpressed in type 2 diabetes mellitusThe EMBO Journal, 1998
- MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclX L and initiates cell deathProceedings of the National Academy of Sciences, 1997
- I-FLICE, a Novel Inhibitor of Tumor Necrosis Factor Receptor-1- and CD-95-induced ApoptosisJournal of Biological Chemistry, 1997
- Death effector domain-containing herpesvirus and poxvirus proteins inhibit both Fas- and TNFR1-induced apoptosisProceedings of the National Academy of Sciences, 1997
- Regulation of Neuronal Survival by the Serine-Threonine Protein Kinase AktScience, 1997
- Involvement of MACH, a Novel MORT1/FADD-Interacting Protease, in Fas/APO-1- and TNF Receptor–Induced Cell DeathCell, 1996
- ICE Family Proteases: Mediators of All Apoptotic Cell Death?Immunity, 1996
- FADD/MORT1 Is a Common Mediator of CD95 (Fas/APO-1) and Tumor Necrosis Factor Receptor-induced ApoptosisJournal of Biological Chemistry, 1996
- FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosisCell, 1995
- Epstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death.Proceedings of the National Academy of Sciences, 1993