PMID- 10442631
OWN - NLM
STAT- MEDLINE
DCOM- 19990830
LR  - 20191210
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 31
DP  - 1999 Aug 5
TI  - PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced
      apoptosis.
PG  - 4409-15
AB  - 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.
FAU - Condorelli, G
AU  - Condorelli G
AD  - Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, Federico
      II University of Naples Medical School, Italy.
FAU - Vigliotta, G
AU  - Vigliotta G
FAU - Cafieri, A
AU  - Cafieri A
FAU - Trencia, A
AU  - Trencia A
FAU - Andalo, P
AU  - Andalo P
FAU - Oriente, F
AU  - Oriente F
FAU - Miele, C
AU  - Miele C
FAU - Caruso, M
AU  - Caruso M
FAU - Formisano, P
AU  - Formisano P
FAU - Beguinot, F
AU  - Beguinot F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, CD)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (FADD protein, human)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (PEA15 protein, human)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Antigens, CD/*physiology
MH  - Apoptosis/*physiology
MH  - Apoptosis Regulatory Proteins
MH  - Breast Neoplasms
MH  - Carrier Proteins/metabolism
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/metabolism
MH  - Fas-Associated Death Domain Protein
MH  - Female
MH  - HeLa Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mutagenesis, Site-Directed
MH  - Phosphoproteins/genetics/*metabolism
MH  - Protein Biosynthesis
MH  - Protein Kinase C/antagonists & inhibitors/metabolism
MH  - Receptors, Tumor Necrosis Factor/*physiology
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Recombinant Proteins/metabolism
MH  - Sequence Deletion
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - fas Receptor/*physiology
EDAT- 1999/08/12 00:00
MHDA- 1999/08/12 00:01
CRDT- 1999/08/12 00:00
PHST- 1999/08/12 00:00 [pubmed]
PHST- 1999/08/12 00:01 [medline]
PHST- 1999/08/12 00:00 [entrez]
AID - 10.1038/sj.onc.1202831 [doi]
PST - ppublish
SO  - Oncogene. 1999 Aug 5;18(31):4409-15. doi: 10.1038/sj.onc.1202831.