PMID- 10235259
OWN - NLM
STAT- MEDLINE
DCOM- 19990614
LR  - 20171116
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 398
IP  - 6730
DP  - 1999 Apr 29
TI  - The CED-4-homologous protein FLASH is involved in Fas-mediated activation of
      caspase-8 during apoptosis.
PG  - 777-85
AB  - Fas is a cell-surface receptor molecule that relays apoptotic (cell death)
      signals into cells. When Fas is activated by binding of its ligand, the
      proteolytic protein caspase-8 is recruited to a signalling complex known as DISC 
      by binding to a Fas-associated adapter protein. A large new protein, FLASH, has
      now been identified by cloning of its complementary DNA. This protein contains a 
      motif with oligomerizing activity whose sequence is similar to that of the
      Caenorhabditis elegans protein CED-4, and another domain (DRD domain) that
      interacts with a death-effector domain in caspase-8 or in the adapter protein.
      Stimulated Fas binds FLASH, so FLASH is probably a component of the DISC
      signalling complex. Transient expression of FLASH activates caspase-8, whereas
      overexpression of a truncated form of FLASH containing only one of its DRD or
      CED-4-like domains does not allow activation of caspase-8 and Fas-mediated
      apoptosis to occur. Overexpression of full-length FLASH blocks the anti-apoptotic
      effect of the adenovirus protein E1B19K. FLASH is therefore necessary for the
      activation of caspase-8 in Fas-mediated apoptosis.
FAU - Imai, Y
AU  - Imai Y
AD  - Institute for Virus Research, Kyoto University, Japan.
FAU - Kimura, T
AU  - Kimura T
FAU - Murakami, A
AU  - Murakami A
FAU - Yajima, N
AU  - Yajima N
FAU - Sakamaki, K
AU  - Sakamaki K
FAU - Yonehara, S
AU  - Yonehara S
LA  - eng
SI  - GENBANK/AF132726
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adenovirus E1 Proteins)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (CASP8AP2 protein, human)
RN  - 0 (Caenorhabditis elegans Proteins)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Casp8ap2 protein, mouse)
RN  - 0 (Ced-4 protein, C elegans)
RN  - 0 (FADD protein, human)
RN  - 0 (Fadd protein, mouse)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Helminth Proteins)
RN  - 0 (Macromolecular Substances)
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, mouse)
RN  - EC 3.4.22.- (Casp9 protein, mouse)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
CIN - Nature. 1999 Apr 29;398(6730):756-7. PMID: 10235255
CIN - Nature. 1999 Oct 14;401(6754):662; discussion 662-3. PMID: 10537104
EIN - Nature 1999 Jul 1;400(6739):89
MH  - *Adaptor Proteins, Signal Transducing
MH  - Adenovirus E1 Proteins/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Apoptosis Regulatory Proteins
MH  - Caenorhabditis elegans
MH  - *Caenorhabditis elegans Proteins
MH  - Calcium-Binding Proteins/*chemistry/genetics/*physiology
MH  - Carrier Proteins/metabolism
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/*metabolism
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Consensus Sequence
MH  - Enzyme Activation
MH  - Fas-Associated Death Domain Protein
MH  - Helminth Proteins/*chemistry
MH  - Humans
MH  - Jurkat Cells
MH  - Macromolecular Substances
MH  - Mice
MH  - Molecular Sequence Data
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction
MH  - fas Receptor/*physiology
EDAT- 1999/05/11 02:03
MHDA- 2001/03/23 10:01
CRDT- 1999/05/11 02:03
PHST- 1999/05/11 02:03 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/05/11 02:03 [entrez]
AID - 10.1038/19709 [doi]
PST - ppublish
SO  - Nature. 1999 Apr 29;398(6730):777-85. doi: 10.1038/19709.