Nature Cell Biology4, 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
1
Division of Biology and the Cancer Center 9500 Gilman Drive 0322, University of California, San Diego, La Jolla, California 92093-0322, USA
2
Current address: AmProx Incorporated, 2120 Las Palmas Drive, Suite F, Carlsbad, California 92009, USA
3
These authors contributed equally to this work
Correspondence should be addressed to Jean Y. J. Wang jywang@ucsd.edu
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.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
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.
-induced apoptosis in murine cells
