PMID- 10521396
OWN - NLM
STAT- MEDLINE
DCOM- 19991118
LR  - 20190516
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 13
IP  - 19
DP  - 1999 Oct 1
TI  - Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced
      apoptosis.
PG  - 2514-26
AB  - Although the molecular mechanisms of TNF signaling have been largely elucidated, 
      the principle that regulates the balance of life and death is still unknown. We
      report here that the death domain kinase RIP, a key component of the TNF
      signaling complex, was cleaved by Caspase-8 in TNF-induced apoptosis. The
      cleavage site was mapped to the aspartic acid at position 324 of RIP. We
      demonstrated that the cleavage of RIP resulted in the blockage of TNF-induced
      NF-kappaB activation. RIPc, one of the cleavage products, enhanced interaction
      between TRADD and FADD/MORT1 and increased cells' sensitivity to TNF. Most
      importantly, the Caspase-8 resistant RIP mutants protected cells against
      TNF-induced apopotosis. These results suggest that cleavage of RIP is an
      important process in TNF-induced apoptosis. Further more, RIP cleavage was also
      detected in other death receptor-mediated apoptosis. Therefore, our study
      provides a potential mechanism to convert cells from life to death in death
      receptor-mediated apoptosis.
FAU - Lin, Y
AU  - Lin Y
AD  - Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical
      Sciences, National Cancer Institute, National Institutes of Health, Bethesda,
      Maryland 20892, USA.
FAU - Devin, A
AU  - Devin A
FAU - Rodriguez, Y
AU  - Rodriguez Y
FAU - Liu, Z G
AU  - Liu ZG
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (FADD protein, human)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (TNF Receptor-Associated Factor 1)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (RIPK1 protein, human)
RN  - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)
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  - *Apoptosis/drug effects
MH  - Apoptosis Regulatory Proteins
MH  - Aspartic Acid
MH  - Binding Sites
MH  - Carrier Proteins/metabolism
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/*metabolism
MH  - Cell Line, Transformed
MH  - Fas-Associated Death Domain Protein
MH  - HeLa Cells
MH  - Humans
MH  - Membrane Glycoproteins/metabolism
MH  - NF-kappa B/metabolism
MH  - Protein Kinases/*metabolism
MH  - Proteins/*metabolism
MH  - Receptor-Interacting Protein Serine-Threonine Kinases
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - TNF Receptor-Associated Factor 1
MH  - TNF-Related Apoptosis-Inducing Ligand
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
PMC - PMC317073
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1101/gad.13.19.2514 [doi]
PST - ppublish
SO  - Genes Dev. 1999 Oct 1;13(19):2514-26. doi: 10.1101/gad.13.19.2514.