Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis

  title={Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis},
  author={Jeehyeon Bae and Sheau Yu Teddy Hsu and Chandra P. Leo and Karen Zell and Aaron J W Hsueh},
Survival factors activate kinases which, in turn, phosphorylate the proapoptotic Bcl-xl/Bcl-2-associated death promoter homolog (BAD) protein at key serine residues. Phosphorylated BAD interacts with 14-3-3 proteins, and overexpression of 14-3-3 attenuates BAD-mediated apoptosis. Although BAD is known to interact with Bcl-2, Bcl-w, and Bcl-xL, the exact relationship between BAD and anti- or proapoptotic Bcl-2 proteins has not been analyzed systematically. Using the yeast two-hybrid protein… 

Antiapoptotic potency of Bcl-2 proteins primarily relies on their stability, not binding selectivity.

The first complete, quantitative cellular interaction profile of all human prosurvival Bcl-2 proteins with all their proapoptotic relatives is established and concludes that clinical diagnostics should include all family members and should be performed at the protein rather than at the messenger RNA level.

New insights in the role of Bcl-2 Bcl-2 and the endoplasmic reticulum

The oncogenic protein Bcl-2 which is expressed in membranes of different subcellular organelles protects cells from apoptosis induced by endogenic stimuli and is able to interact with the endoplasmic protein Bap31 thus avoiding caspase activation at the ER.

Activation of Bad trafficking is involved in the BCR-mediated apoptosis of immature B cells

It is suggested that differences in intracellular Bad trafficking may be involved in the differential outcome of BCR signaling and suggest that sequestration of Bad within subcellular compartments may be a new mechanism of apoptosis regulation.

A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells

The major role of Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells is emphasized, with a marked reduced apoptosis uponIL-6 starvation compared to HMCLs transduced with control GFP retrovirus and may grow without adding IL- 6.

Chemosensitization of prostate cancer by modulating Bcl-2 family proteins.

The future may lie in targeting multiple steps of the apoptotic pathway, including Bcl-2/xL/Mcl-1, to debilitate the survival capacity of cancer cells and make chemotherapy induced death their only option.

Calcineurin-mediated Bad translocation regulates cyanide-induced neuronal apoptosis.

By inducing a rapid increase in cytosolic free Ca2+, cyanide can partially initiate the apoptotic cascade through a calcineurin-mediated translocation of Bad to mitochondria.



BH3 Domain of BAD Is Required for Heterodimerization with BCL-XL and Pro-apoptotic Activity*

It is reported here that deletion mapping and site-directed mutagenesis identified a BH3 domain within BAD that proved necessary for both its heterodimerization with BCL-XL and its death agonist activity.

Interference of BAD (Bcl-xL/Bcl-2-associated death promoter)-induced apoptosis in mammalian cells by 14-3-3 isoforms and P11.

The present findings suggest that BAD plays an important role in mediating communication between different signal transduction pathways regulated by hormonal signals and the apoptotic mechanism controlled by Bcl-2 family members.

p21-Activated Kinase 1 Phosphorylates the Death Agonist Bad and Protects Cells from Apoptosis

ABSTRACT Bad is a critical regulatory component of the intrinsic cell death machinery that exerts its death-promoting effect upon heterodimerization with the antiapoptotic proteins Bcl-2 and Bcl-xL.

Survival activity of Bcl-2 homologs Bcl-w and A1 only partially correlates with their ability to bind pro-apoptotic family members

It is suggested that certain pro-apoptotic proteins may also contribute to apoptosis by a mechanism independent of binding pro-survival proteins.

Blk, a BH3-containing Mouse Protein That Interacts with Bcl-2 and Bcl-xL, Is a Potent Death Agonist*

A novel murine member of the pro-apoptotic Bcl-2 family, designated Blk, is structurally and functionally related to human Bik and localized to the mitochondrial membrane, suggesting that Blk induces apoptosis through activation of the cytochromec-Apaf-1-caspase-9 pathway.

Adenovirus E1B 19-kDa Death Suppressor Protein Interacts with Bax but Not with Bad*

It is shown that the analogous mutation in BH1 of 19K also abrogates the anti-apoptotic properties of 18K and its ability to interact with Bax, thus establishing the critical importance of this residue within BH 1 and the likely similarity of Bcl-2 and 19K function.

Bok is a pro-apoptotic Bcl-2 protein with restricted expression in reproductive tissues and heterodimerizes with selective anti-apoptotic Bcl-2 family members.

Identification of Bok as a new pro-apoptotic Bcl-2 protein with restricted tissue distribution and heterodimerization properties could facilitate elucidation of apoptosis mechanisms in reproductive tissues undergoing hormone-regulated cyclic cell turnover.

Regulation of BAD by cAMP-dependent protein kinase is mediated via phosphorylation of a novel site, Ser155.

Ser(155) is identified as a third phosphorylation site on BAD and is the only residue in BAD that becomes phosphorylated when cells are exposed to cAMP-elevating agents, and prevents it from binding to Bcl-X(L) and promotes its interaction with 14-3-3 proteins.