Article abstract
Nature Cell Biology 4, 757 - 765 (2002)
Published online: 23 September 2002 | doi:10.1038/ncb853
Signal-dependent protection from apoptosis in mice expressing caspase-resistant Rb
B. Nelson Chau1,3, Helena Lobo Borges1,3, Tung-Ti Chen2, Anja Masselli1, Irina C. Hunton1 & Jean Y. J. Wang1
Abstract
The retinoblastoma tumour suppressor protein RB is cleaved by caspases during apoptosis. Here we have mutated the caspase cleavage site in the carboxy terminus of the murine Rb protein in the mouse germ line to create the Rb-MI allele. After endotoxic shock, expression of Rb-MI inhibits apoptosis in the intestines, but not in the spleen, and promotes the survival of male mice. Fibroblasts expressing Rb-MI protein are protected from apoptosis induced by the tumour-necrosis factor-
type I receptor (TNFRI) but remain sensitive to cell death induced by DNA damage. Correspondingly, the release of cytochrome c and the activation of caspase-3 induced by TNFRI, but not by DNA damage, are defective in cells expressing Rb-MI. Our results highlight the importance of Rb cleavage in TNFRI-induced apoptosis.
- Division of Biology and the Cancer Center 9500 Gilman Drive 0322, University of California, San Diego, La Jolla, California 92093-0322, USA
- Current address: AmProx Incorporated, 2120 Las Palmas Drive, Suite F, Carlsbad, California 92009, USA
- These authors contributed equally to this work
Correspondence to: Jean Y. J. Wang1 e-mail: jywang@ucsd.edu
|
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated REVIEWS NEWS AND VIEWS RESEARCH |
