Inhibition of ubiquitin-mediated degradation of MOAP-1 by apoptotic stimuli promotes Bax function in mitochondria
- 12 June 2007
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (24), 10051-10056
- https://doi.org/10.1073/pnas.0700007104
Abstract
The multidomain proapoptotic protein Bax of the Bcl-2 family is a central regulator for controlling the release of apoptogenic factors from mitochondria. Recent evidence suggests that the Bax-associating protein MOAP-1 may act as an effector for promoting Bax function in mitochondria. Here, we report that MOAP-1 protein is rapidly up-regulated by multiple apoptotic stimuli in mammalian cells. MOAP-1 is a short-lived protein (t(1/2) approximately 25 min) that is constitutively degraded by the ubiquitin-proteasome system. Induction of MOAP-1 by apoptotic stimuli ensues through inhibition of its polyubiquitination process. Elevation of MOAP-1 levels sensitizes cells to apoptotic stimuli and promotes recombinant Bax-mediated cytochrome c release from isolated mitochondria. Mitochondria depleted of short-lived proteins by cycloheximide (CHX) become resistant to Bax-mediated cytochrome c release. Remarkably, incubation of these mitochondria with in vitro-translated MOAP-1 effectively restores the cytochrome c releasing effect of recombinant Bax. We propose that apoptotic stimuli can facilitate the proapoptotic function of Bax in mitochondria through stabilization of MOAP-1.This publication has 37 references indexed in Scilit:
- The Pathophysiology of Mitochondrial Cell DeathScience, 2004
- The proteasome: a suitable antineoplastic targetNature Reviews Cancer, 2004
- Caspase Activation Inhibits Proteasome Function during ApoptosisMolecular Cell, 2004
- PROTEINS OF THE BCL‐2 FAMILY IN APOPTOSIS SIGNALLING: FROM MECHANISTIC INSIGHTS TO THERAPEUTIC OPPORTUNITIESClinical and Experimental Pharmacology and Physiology, 2004
- In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2Science, 2004
- Cell Death: Critical Control PointsCell, 2004
- Back to the Future with UbiquitinCell, 2004
- HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53Proceedings of the National Academy of Sciences of the United States of America, 2003
- Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiationGenes & Development, 2003
- Deadly encounter: ubiquitin meets apoptosisNature Reviews Molecular Cell Biology, 2002