PMID- 10200473
OWN - NLM
STAT- MEDLINE
DCOM- 19990511
LR  - 20171116
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 5
IP  - 4
DP  - 1998 Apr
TI  - Cell death attenuation by 'Usurpin', a mammalian DED-caspase homologue that
      precludes caspase-8 recruitment and activation by the CD-95 (Fas, APO-1) receptor
      complex.
PG  - 271-88
AB  - Apoptotic cell suicide initiated by ligation of CD95 (Fas/APO-1) occurs through
      recruitment, oligomerization and autocatalytic activation of the cysteine
      protease, caspase-8 (MACH, FLICE, Mch5). An endogenous mammalian regulator of
      this process, named Usurpin, has been identified (aliases for Usurpin include
      CASH, Casper, CLARP, FLAME-1, FLIP, I-FLICE and MRIT). This protein is
      ubiquitously expressed and exists as at least three isoforms arising by
      alternative mRNA splicing. The Usurpin gene is comprised of 13 exons and is
      clustered within approximately 200 Kb with the caspase-8 and -10 genes on human
      chromosome 2q33-34. The Usurpin polypeptide has features in common with
      pro-caspase-8 and -10, including tandem 'death effector domains' on the
      N-terminus of a large subunit/small subunit caspase-like domain, but it lacks key
      residues that are necessary for caspase proteolytic activity, including the His
      and Cys which form the catalytic substrates diad, and residues that stabilize the
      P1 aspartic acid in substrates. Retro-mutation of these residues to functional
      caspase counterparts failed to restore proteolytic activity, indicating that
      other determinants also ensure the absence of catalytic potential. Usurpin
      heterodimerized with pro-caspase-8 in vitro and precluded pro-caspase-8
      recruitment by the FADD/MORT1 adapter protein. Cell death induced by CD95
      (Fas/APO-1) ligation was attenuated in cells transfected with Usurpin. In vivo, a
      Usurpin deficit was found in cardiac infarcts where TUNEL-positive myocytes and
      active caspase-3 expression were prominent following ischemia/reperfusion injury.
      In contrast, abundant Usurpin expression (and a caspase-3 deficit) occurred in
      surrounding unaffected cardiac tissue, suggesting reciprocal regulation of these 
      pro- and anti-apoptotic molecules in vivo. Usurpin thus appears to be an
      endogenous modulator of apoptosis sensitivity in mammalian cells, including the
      susceptibility of cardiac myocytes to apoptotic death following ischemia/
      reperfusion injury.
FAU - Rasper, D M
AU  - Rasper DM
AD  - Department of Biochemistry and Molecular Biology, Merck Frosst Centre for
      Therapeutic Research, Pointe Claire-Dorval, Quebec, Canada, H9R 4P8.
FAU - Vaillancourt, J P
AU  - Vaillancourt JP
FAU - Hadano, S
AU  - Hadano S
FAU - Houtzager, V M
AU  - Houtzager VM
FAU - Seiden, I
AU  - Seiden I
FAU - Keen, S L
AU  - Keen SL
FAU - Tawa, P
AU  - Tawa P
FAU - Xanthoudakis, S
AU  - Xanthoudakis S
FAU - Nasir, J
AU  - Nasir J
FAU - Martindale, D
AU  - Martindale D
FAU - Koop, B F
AU  - Koop BF
FAU - Peterson, E P
AU  - Peterson EP
FAU - Thornberry, N A
AU  - Thornberry NA
FAU - Huang, J
AU  - Huang J
FAU - MacPherson, D P
AU  - MacPherson DP
FAU - Black, S C
AU  - Black SC
FAU - Hornung, F
AU  - Hornung F
FAU - Lenardo, M J
AU  - Lenardo MJ
FAU - Hayden, M R
AU  - Hayden MR
FAU - Roy, S
AU  - Roy S
FAU - Nicholson, D W
AU  - Nicholson DW
LA  - eng
SI  - GENBANK/AF015450
SI  - GENBANK/AF015451
SI  - GENBANK/AF015452
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (CASP8 and FADD-Like Apoptosis Regulating Protein)
RN  - 0 (CFLAR protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (fas Receptor)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Casp8 protein, rat)
RN  - EC 3.4.22.- (Casp9 protein, rat)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apoptosis/genetics/immunology/*physiology
MH  - Base Sequence
MH  - CASP8 and FADD-Like Apoptosis Regulating Protein
MH  - Carrier Proteins/genetics/physiology
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/genetics/*physiology
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 2/genetics
MH  - Cloning, Molecular
MH  - DNA Primers/genetics
MH  - Enzyme Activation
MH  - Female
MH  - HeLa Cells
MH  - Humans
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Jurkat Cells
MH  - Male
MH  - Models, Biological
MH  - Molecular Sequence Data
MH  - Myocardial Reperfusion Injury/genetics/pathology/physiopathology
MH  - Pregnancy
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Sequence Homology, Amino Acid
MH  - Tissue Distribution
MH  - fas Receptor/*physiology
EDAT- 1999/04/14 00:00
MHDA- 1999/04/14 00:01
CRDT- 1999/04/14 00:00
PHST- 1999/04/14 00:00 [pubmed]
PHST- 1999/04/14 00:01 [medline]
PHST- 1999/04/14 00:00 [entrez]
AID - 10.1038/sj.cdd.4400370 [doi]
PST - ppublish
SO  - Cell Death Differ. 1998 Apr;5(4):271-88. doi: 10.1038/sj.cdd.4400370.