PMID- 12010809
OWN - NLM
STAT- MEDLINE
DCOM- 20020701
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 99
IP  - 11
DP  - 2002 Jun 1
TI  - Characterization of caspase-8L: a novel isoform of caspase-8 that behaves as an 
      inhibitor of the caspase cascade.
PG  - 4070-8
AB  - Caspase-8 (Fas-associating protein with death domain-like interleukin-1beta- 
      converting enzyme [FLICE]/MACH/Mch5) belongs to a family of cysteine proteases 
      presumed to be the apex of the apoptotic signaling pathways. We recently reported 
      the presence of a novel isoform of caspase-8, named caspase-8L, generated by the 
      alternative splicing of human caspase-8 gene, from human peripheral blood 
      lymphocytes by reverse transcriptase-polymerase chain reaction. We herein report 
      a functional analysis of caspase-8L in the Fas-mediated apoptotic pathway. 
      Caspase-8L is missing the catalytic site of caspase-8 but retains 2 N-terminal 
      repeats of the death-effector domain. The caspase-8L messenger RNA was detected 
      in various tissues but not in any cell lines examined. In human peripheral blood 
      lymphocytes, caspase-8L was strongly suggested to be expressed at the protein 
      level. In MCF-7 cells, caspase-8L transfection itself did not affect cell 
      viability but instead inhibited the apoptosis induced by the cotransfection of 
      caspase-8 in a dominant negative manner. Moreover, Fas-mediated apoptosis was 
      inhibited in caspase-8L-transfected Jurkat cells, which were associated with a 
      reduction in the caspase-8 catalytic activity. In vitro binding assays 
      demonstrated that caspase-8L bound to FADD (Fas-associating protein with death 
      domain) and caspase-8a and blocked the binding of caspase-8 to FADD. In in vivo 
      binding assays, transfected caspase-8L bound to endogenous FADD. Thus, caspase-8L 
      acts as an inhibitor of caspase-8 by interfering with the binding of caspase-8 to 
      FADD and is involved in the regulation of Fas-mediated apoptosis.
FAU - Himeji, Daisuke
AU  - Himeji D
AD  - Medicine and Biosystemic Science, Kyushu University Graduate School of Medical 
      Sciences, Japan.
FAU - Horiuchi, Takahiko
AU  - Horiuchi T
FAU - Tsukamoto, Hiroshi
AU  - Tsukamoto H
FAU - Hayashi, Kenshi
AU  - Hayashi K
FAU - Watanabe, Takeshi
AU  - Watanabe T
FAU - Harada, Mine
AU  - Harada M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Caspase Inhibitors)
RN  - 0 (DNA, Complementary)
RN  - 0 (Isoenzymes)
RN  - 0 (Recombinant Proteins)
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.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Apoptosis
MH  - Breast Neoplasms
MH  - COS Cells
MH  - Caspase 8
MH  - Caspase 9
MH  - *Caspase Inhibitors
MH  - Caspases/chemistry/*genetics/metabolism
MH  - Chlorocebus aethiops
MH  - Cloning, Molecular
MH  - DNA, Complementary
MH  - Female
MH  - Genetic Vectors
MH  - Humans
MH  - Isoenzymes/chemistry/genetics/metabolism
MH  - Lymphocytes/cytology/enzymology/immunology
MH  - Molecular Sequence Data
MH  - Protein Biosynthesis
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured
MH  - fas Receptor/immunology
EDAT- 2002/05/16 10:00
MHDA- 2002/07/02 10:01
CRDT- 2002/05/16 10:00
PHST- 2002/05/16 10:00 [pubmed]
PHST- 2002/07/02 10:01 [medline]
PHST- 2002/05/16 10:00 [entrez]
AID - S0006-4971(20)60782-0 [pii]
AID - 10.1182/blood.v99.11.4070 [doi]
PST - ppublish
SO  - Blood. 2002 Jun 1;99(11):4070-8. doi: 10.1182/blood.v99.11.4070.