RGD Reference Report - BH3-only proteins in apoptosis and beyond: an overview. - Rat Genome Database

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BH3-only proteins in apoptosis and beyond: an overview.

Authors: Lomonosova, E  Chinnadurai, G 
Citation: Lomonosova E and Chinnadurai G, Oncogene. 2008 Dec;27 Suppl 1:S2-19.
RGD ID: 2314029
Pubmed: PMID:19641503   (View Abstract at PubMed)
PMCID: PMC2928556   (View Article at PubMed Central)
DOI: DOI:10.1038/onc.2009.39   (Journal Full-text)

BH3-only BCL-2 family proteins are effectors of canonical mitochondrial apoptosis. They discharge their pro-apoptotic functions through BH1-3 pro-apoptotic proteins such as BAX and BAK, while their activity is suppressed by BH1-4 anti-apoptotic BCL-2 family members. The precise mechanism by which BH3-only proteins mediate apoptosis remains unresolved. The existing data are consistent with three mutually non-exclusive models (1) displacement of BH1-3 proteins from complexes with BH1-4 proteins; (2) direct interaction with and conformational activation of BH1-3 proteins; and (3) membrane insertion and membrane remodeling. The BH3-only proteins appear to play critical roles in restraining cancer and inflammatory diseases such as rheumatoid arthritis. Molecules that mimic the effect of BH3-only proteins are being used in treatments against these diseases. The cell death activity of a subclass of BH3-only members (BNIP3 and BNIP3L) is linked to cardiomyocyte loss during heart failure. In addition to their established role in apoptosis, several BH3-only members also regulate diverse cellular functions in cell-cycle regulation, DNA repair and metabolism. Several members are implicated in the induction of autophagy and autophagic cell death, possibly through unleashing of the BH3-only autophagic effector Beclin 1 from complexes with BCL-2/BCL-xL. The Chapters included in the current Oncogene Review issues provide in-depth discussions on various aspects of major BH3-only proteins.

Objects Annotated

Genes (Rattus norvegicus)
Bad  (BCL2-associated agonist of cell death)
Bbc3  (Bcl-2 binding component 3)
Bcl2l11  (Bcl2-like 11)
Bid  (BH3 interacting domain death agonist)
Bik  (BCL2-interacting killer)
Bmf  (Bcl2 modifying factor)
Bnip1  (BCL2 interacting protein 1)
Bnip3  (BCL2 interacting protein 3)
Bnip3l  (BCL2 interacting protein 3 like)
Hrk  (harakiri, BCL2 interacting protein)
Pmaip1  (phorbol-12-myristate-13-acetate-induced protein 1)

Genes (Mus musculus)
Bad  (BCL2-associated agonist of cell death)
Bbc3  (BCL2 binding component 3)
Bcl2l11  (BCL2 like 11)
Bid  (BH3 interacting domain death agonist)
Bik  (BCL2-interacting killer)
Bmf  (BCL2 modifying factor)
Bnip1  (BCL2/adenovirus E1B interacting protein 1)
Bnip3  (BCL2/adenovirus E1B interacting protein 3)
Bnip3l  (BCL2/adenovirus E1B interacting protein 3-like)
Hrk  (harakiri, BCL2 interacting protein (contains only BH3 domain))
Pmaip1  (phorbol-12-myristate-13-acetate-induced protein 1)

Genes (Homo sapiens)
BAD  (BCL2 associated agonist of cell death)
BBC3  (BCL2 binding component 3)
BCL2L11  (BCL2 like 11)
BID  (BH3 interacting domain death agonist)
BIK  (BCL2 interacting killer)
BMF  (Bcl2 modifying factor)
BNIP1  (BCL2 interacting protein 1)
BNIP3  (BCL2 interacting protein 3)
BNIP3L  (BCL2 interacting protein 3 like)
HRK  (harakiri, BCL2 interacting protein)
PMAIP1  (phorbol-12-myristate-13-acetate-induced protein 1)


Additional Information