pRb/E2F-1-mediated caspase-dependent induction of Noxa amplifies the apoptotic effects of the Bcl-2/Bcl-xL inhibitor ABT-737 - Archive ouverte HAL Access content directly
Journal Articles Cell Death and Differentiation Year : 2013

pRb/E2F-1-mediated caspase-dependent induction of Noxa amplifies the apoptotic effects of the Bcl-2/Bcl-xL inhibitor ABT-737

(1) , (1) , (1) , (1) , (1) , (1) , (1)
1

Abstract

Although Bcl-2 family members control caspase activity by regulating mitochondrial permeability, caspases can, in turn, amplify the apoptotic process upstream of mitochondria by ill-characterized mechanisms. We herein show that treatment with a potent inhibitor of Bcl-2 and Bcl-xL, ABT-737, triggers caspase-dependent induction of the BH3-only protein, Mcl-1 inhibitor, Noxa. RNA interference experiments reveal that induction of Noxa, and subsequent cell death, rely not only on the transcription factor E2F-1 but also on its regulator pRb. In response to ABT-737, pRb is cleaved by caspases into a p68Rb form that still interacts with E2F-1. Moreover, pRb occupies the noxa promoter together with E2F-1, in a caspase-dependent manner upon ABT-737 treatment. Thus, caspases contribute to trigger the mitochondrial apoptotic pathway by coupling Bcl-2/Bcl-xL inhibition to that of Mcl-1, via the pRb/E2F-1-dependent induction of Noxa.

Dates and versions

inserm-02447042 , version 1 (21-01-2020)

Identifiers

Cite

Joséphine Bertin-Ciftci, B Barré, J Le Pen, Laurent A Maillet, C Couriaud, et al.. pRb/E2F-1-mediated caspase-dependent induction of Noxa amplifies the apoptotic effects of the Bcl-2/Bcl-xL inhibitor ABT-737. Cell Death and Differentiation, 2013, 20 (5), pp.755 - 764. ⟨10.1038/cdd.2013.6⟩. ⟨inserm-02447042⟩
44 View
1 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More