• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

The two opposite signaling pathways that stimulate NF-kappaB 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-kappaB activation. The uncleavable RIPD324A mutant was less apoptotic, but its ability to activate NF-kappaB activation was greater than the wild type counterpart. Ectopic expression of the pro-apoptotic C-terminal fragment of RIP inhibited TNF-induced NF-kappaB activation by suppressing the activity of I-kappaB kinasebeta (IKKbeta) which phosphorylates I-kB, an inhibitor of NF-kappaB, 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-kappaB activation, and thereby amplifies the activation of caspase-8 which initiates the downstream apoptotic events. Oncogene (2000) 19, 4491 - 4499.

Pubmed ID: 11002422

Authors

  • Kim JW
  • Choi EJ
  • Joe CO

Journal

Oncogene

Publication Data

September 14, 2000

Associated Grants

None

Mesh Terms

  • Antigens, CD
  • Apoptosis
  • Arabidopsis Proteins
  • Caspase 8
  • Caspase 9
  • Caspases
  • Cell Death
  • Cell Line
  • Fatty Acid Desaturases
  • Humans
  • I-kappa B Kinase
  • NF-kappa B
  • Peptide Fragments
  • Protein-Serine-Threonine Kinases
  • Proteins
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Signal Transduction
  • Tumor Necrosis Factor-alpha