Article

IBRDC2, an IBR-type E3 ubiquitin ligase, is a regulatory factor for Bax and apoptosis activation.

Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, MD, USA.
The EMBO Journal (impact factor: 9.2). 03/2010; 29(8):1458-71. DOI:10.1038/emboj.2010.39 pp.1458-71
Source: PubMed

ABSTRACT Bax, a pro-apoptotic protein from the Bcl-2 family, is central to apoptosis regulation. To suppress spontaneous apoptosis, Bax must be under stringent control that may include regulation of Bax conformation and expression levels. We report that IBRDC2, an IBR-type RING-finger E3 ubiquitin ligase, regulates the levels of Bax and protects cells from unprompted Bax activation and cell death. Downregulation of IBRDC2 induces increased cellular levels and accumulation of the active form of Bax. The ubiquitination-dependent regulation of Bax stability is suppressed by IBRDC2 downregulation and stimulated by IBRDC2 overexpression in both healthy and apoptotic cells. Although mostly cytosolic in healthy cells, upon induction of apoptosis, IBRDC2 accumulates in mitochondrial domains enriched with Bax. Mitochondrial accumulation of IBRDC2 occurs in parallel with Bax activation and also depends on the expression levels of Bcl-xL. Furthermore, IBRDC2 physically interacts with activated Bax. By applying Bax mutants in HCT116 Bax(-/-) cells, combined with the use of active Bax-specific antibodies, we have established that both mitochondrial localization and apoptotic activation of Bax are required for IBRDC2 translocation to the mitochondria.

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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

activated Bax
 
active Bax-specific antibodies
 
apoptotic activation
 
apoptotic cells
 
applying Bax mutants
 
Bax activation
 
Bcl-2 family
 
cellular levels
 
healthy cells
 
IBR-type RING-finger E3 ubiquitin ligase
 
IBRDC2 accumulates
 
IBRDC2 downregulation
 
IBRDC2 overexpression
 
IBRDC2 translocation
 
Mitochondrial accumulation
 
mitochondrial domains enriched
 
mitochondrial localization
 
pro-apoptotic protein
 
spontaneous apoptosis
 
unprompted Bax activation