PMID- 10958661
OWN - NLM
STAT- MEDLINE
DCOM- 20000922
LR  - 20220331
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 20
IP  - 18
DP  - 2000 Sep
TI  - The death domain kinase RIP is essential for TRAIL (Apo2L)-induced activation of 
      IkappaB kinase and c-Jun N-terminal kinase.
PG  - 6638-45
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) (Apo2 
      ligand [Apo2L]) is a member of the TNF superfamily and has been shown to have 
      selective antitumor activity. Although it is known that TRAIL (Apo2L) induces 
      apoptosis and activates NF-kappaB and Jun N-terminal kinase (JNK) through 
      receptors such as TRAIL-R1 (DR4) and TRAIL-R2 (DR5), the components of its 
      signaling cascade have not been well defined. In this report, we demonstrated 
      that the death domain kinase RIP is essential for TRAIL-induced IkappaB kinase 
      (IKK) and JNK activation. We found that ectopic expression of the dominant 
      negative mutant RIP, RIP(559-671), blocks TRAIL-induced IKK and JNK activation. 
      In the RIP null fibroblasts, TRAIL failed to activate IKK and only partially 
      activated JNK. The endogenous RIP protein was detected by immunoprecipitation in 
      the TRAIL-R1 complex after TRAIL treatment. More importantly, we found that RIP 
      is not involved in TRAIL-induced apoptosis. In addition, we also demonstrated 
      that the TNF receptor-associated factor 2 (TRAF2) plays little role in 
      TRAIL-induced IKK activation although it is required for TRAIL-mediated JNK 
      activation. These results indicated that the death domain kinase RIP, a key 
      factor in TNF signaling, also plays a pivotal role in TRAIL-induced IKK and JNK 
      activation.
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 - Cook, A
AU  - Cook A
FAU - Keane, M M
AU  - Keane MM
FAU - Kelliher, M
AU  - Kelliher M
FAU - Lipkowitz, S
AU  - Lipkowitz S
FAU - Liu, Z G
AU  - Liu ZG
LA  - eng
GR  - R01 GM061298/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Ligands)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Proteins)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFRSF10A protein, human)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tnfsf10 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (RIPK1 protein, human)
RN  - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ripk1 protein, mouse)
RN  - EC 2.7.11.10 (CHUK protein, human)
RN  - EC 2.7.11.10 (Chuk protein, mouse)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - EC 2.7.11.10 (IKBKB protein, human)
RN  - EC 2.7.11.10 (IKBKE protein, human)
RN  - EC 2.7.11.10 (Ikbkb protein, mouse)
RN  - EC 2.7.11.10 (Ikbke protein, mouse)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Apoptosis Regulatory Proteins
MH  - Cell Line
MH  - Enzyme Activation
MH  - Fibroblasts/cytology
MH  - HeLa Cells
MH  - Humans
MH  - I-kappa B Kinase
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Ligands
MH  - Membrane Glycoproteins/genetics/*metabolism
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Mutagenesis
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Proteins/genetics/*metabolism/physiology
MH  - Receptor-Interacting Protein Serine-Threonine Kinases
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Signal Transduction
MH  - TNF Receptor-Associated Factor 2
MH  - TNF-Related Apoptosis-Inducing Ligand
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
PMC - PMC86162
EDAT- 2000/08/25 11:00
MHDA- 2000/09/30 11:01
PMCR- 2000/09/01
CRDT- 2000/08/25 11:00
PHST- 2000/08/25 11:00 [pubmed]
PHST- 2000/09/30 11:01 [medline]
PHST- 2000/08/25 11:00 [entrez]
PHST- 2000/09/01 00:00 [pmc-release]
AID - 0436 [pii]
AID - 10.1128/MCB.20.18.6638-6645.2000 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2000 Sep;20(18):6638-45. doi: 10.1128/MCB.20.18.6638-6645.2000.