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Cited by 836

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Cleavage of the death domain kinase RIP by Caspase-8 prompts TNF-induced apoptosis

Open access
Lin, Y., Devin, A., Rodriguez, Y., Liu, Z.-g.·1999·Genes & Development

Abstract

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.

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Metadata

Authors
Lin, Y., Devin, A., Rodriguez, Y., & Liu, Z.-G.
Venue
Genes & Development
Published
1999-10-01
Volume
13
Issue
19
Pages
2514-2526
ISSN
0890-9369 (ISSN-L)
OpenAlex
W1986978728
Cited by
836
References
7
Type
posted content
Language
en
Open access
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