GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:10442631

From GONUTS
Jump to: navigation, search
Citation

Condorelli, G, Vigliotta, G, Cafieri, A, Trencia, A, Andalò, P, Oriente, F, Miele, C, Caruso, M, Formisano, P and Beguinot, F (1999) PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis. Oncogene 18:4409-15

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 TNFalpha 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-alpha. TNFalpha, 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.

Links

PubMed Online version:10.1038/sj.onc.1202831

Keywords

Adaptor Proteins, Signal Transducing; Antigens, CD/physiology; Antigens, CD95/physiology; Apoptosis/physiology; Breast Neoplasms; Carrier Proteins/metabolism; Caspase 8; Caspase 9; Caspases/metabolism; Fas-Associated Death Domain Protein; Female; HeLa Cells; Humans; Intracellular Signaling Peptides and Proteins; Mutagenesis, Site-Directed; Phosphoproteins/genetics; Phosphoproteins/metabolism; Protein Biosynthesis; Protein Kinase C/antagonists & inhibitors; Protein Kinase C/metabolism; Receptors, Tumor Necrosis Factor/physiology; Receptors, Tumor Necrosis Factor, Type I; Recombinant Proteins/metabolism; Sequence Deletion; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:FADD

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15121

F

Seeded From UniProt

complete

HUMAN:CASP8

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15121

F

Seeded From UniProt

complete

HUMAN:PEA15

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q14790

F

Seeded From UniProt

complete

HUMAN:PEA15

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13158

F

Seeded From UniProt

complete

HUMAN:PEA15

involved_in

GO:1902042: negative regulation of extrinsic apoptotic signaling pathway via death domain receptors

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.