Activation of death inducing signaling complex(DISC) by the pro-apoptotic C terminal fragment of RIP

The two opposite signaling pathways that stimulate NF-kappa B activation and apoptosis are both mediated by tumor necrosis factor receptor 1 (TNFR1) and its cytosolic associated proteins. In this study, we demonstrate that the proteolytic cleavage of receptor interacting protein (RIP) by caspase-8 during TNF-induced apoptosis abrogates the stimulatory role of RIP on TNF-induced NF-kappa B activation. The uncleavable RIPD324A mutant was less apoptotic, but its ability to activate NF-kappa B activation was greater than the wild type counterpart, Ectopic expression of the pro-apoptotic C-terminal fragment of RIP inhibited TNF-induced NF-kappa B activation by suppressing the activity of I-kappa B kinase beta (IKK beta) which phosphorylates I-kappa B, an inhibitor of NF-kappa B, and triggers its ubiquitin-mediated degradation, The C-terminal fragment of RIP also enhanced the association between TNFR1 and death domain proteins including TNFR1 associated death domain (TRADD) and Fas associated death domain (FADD), resulting in the activation of caspase-8 and stimulation of apoptosis, The present study suggest that the C-terminal fragment of RIP produced by caspase-8 activates death-inducing signaling complex (DISC), attenuates NF-kappa B activation, and thereby amplifies the activation of caspase-8 which initiates the downstream apoptotic events.
Publisher
Nature Publishing Group
Issue Date
2000-09
Language
ENG
Keywords

NF-KAPPA-B; NECROSIS-FACTOR RECEPTOR; INDUCED CELL-DEATH; DOMAIN KINASE RIP; CONTAINS 2; IKK-ALPHA; PROTEIN; CLEAVAGE; CD95; PHOSPHORYLATION

Citation

ONCOGENE, v.19, no.39, pp.4491 - 4499

ISSN
0950-9232
URI
http://hdl.handle.net/10203/74778
Appears in Collection
BS-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
  • Hit : 271
  • Download : 0
  • Cited 0 times in thomson ci
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡClick to seewebofscience_button
⊙ Cited 66 items in WoSClick to see citing articles inrecords_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0