Caspase-9 can antagonize p53-induced apoptosis by generating a p76Rb truncated form of Rb - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Oncogene Année : 2005

Caspase-9 can antagonize p53-induced apoptosis by generating a p76Rb truncated form of Rb

Résumé

The tumor suppressor Rb (retinoblastoma protein) is known to regulate p53-dependent apoptosis, but the mechanisms involved are unclear. In a rat fibroblast model, we previously observed that caspase inhibition potentiates p53-dependent apoptosis and prevents the Rb cleavage associated with p53 activation. These results suggested that a caspase(s) can antagonize p53-mediated apoptosis via the production of a protective Rb truncated form. Here, we identify caspase-9 as the caspase that interferes, upstream of the mitochondrion, with p53-induced apoptosis in both immortalized and primary fibroblasts. This caspase can be detected as a p38 processed form in living cells, in the absence of apoptosome formation and apoptotic signal. We also provide evidence that the involvement of caspase-9 in a pre-mitochondrial protective pathway results from the previously undescribed cleavage of Rb, at a LExD site, into a p76(Rb) form, which antagonizes p53-induced apoptosis. These results establish that a truncated form of Rb can display an antiapoptotic activity, rather than just being a by-product of Rb degradation.
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hal-04497207 , version 1 (09-03-2024)

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Christophe Lemaire, Nelly Godefroy, Ioana Costina-Parvu, Vincent Rincheval, Flore Renaud, et al.. Caspase-9 can antagonize p53-induced apoptosis by generating a p76Rb truncated form of Rb. Oncogene, 2005, 24 (20), pp.3297-3308. ⟨10.1038/sj.onc.1208493⟩. ⟨hal-04497207⟩

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