Article

Bcl-2 localized at the nuclear compartment induces apoptosis after transient overexpression.

Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555-1043, USA.
Journal of Biological Chemistry (impact factor: 4.77). 01/2007; 281(52):40493-502. DOI:10.1074/jbc.M606181200 pp.40493-502
Source: PubMed

ABSTRACT Bcl-2 is the best characterized member of a large family of proteins that regulate apoptosis. Although it is established that Bcl-2 localized at the mitochondria functions as an anti-apoptotic protein, the function of Bcl-2 at the nucleus remains unclear. Recently we showed that nuclear compartment-associated Bcl-2 inhibits transcription factor activation. Based on this observation, we hypothesized that presence of Bcl-2 at the nucleus may induce rather than protect cells from apoptosis. Here we investigated the putative apoptotic role of nuclear compartment-associated Bcl-2. Additionally, we examined the role of the Bcl-2 BH4 domain in mediating binding to FKBP38, the Bcl-2 mitochondrial chaperone. Our results demonstrate a novel, pro-apoptotic function for nuclear Bcl-2 and identify the Bcl-2 BH4 domain as a key regulator in mediating Bcl-2/FKBP38 binding. These results indicate that Bcl-2 has a dual role as both a protector and a killer and that the ability to switch roles depends on Bcl-2 subcellular localization.

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Keywords

anti-apoptotic protein
 
Bcl-2
 
Bcl-2 BH4 domain
 
Bcl-2 localized
 
Bcl-2 mitochondrial chaperone
 
Bcl-2 subcellular localization
 
characterized member
 
dual role
 
large family
 
mediating Bcl-2/FKBP38 binding
 
mediating binding
 
mitochondria functions
 
nuclear Bcl-2
 
nuclear compartment-associated Bcl-2
 
nuclear compartment-associated Bcl-2 inhibits transcription factor activation
 
pro-apoptotic function
 
protector
 
putative apoptotic role
 
regulate apoptosis
 
roles