Editors' ChoiceApoptosis

Pathway Intersection at BAR

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Science's STKE  21 Mar 2000:
Vol. 2000, Issue 24, pp. tw13
DOI: 10.1126/stke.2000.24.tw13

Apoptosis can be inititated either at the cell surface, through activation of tumor necrosis factor (TNF)-family receptors such as Fas, or intracellularly at the mitchondria.TNF receptors form a death-inducing protein complex containing the adaptor protein Fadd and procaspases, both of which have a protein interaction module called the death effector domain (DED). Caspase activation also results when the Bcl-2 family member Bax induces release of cytochrome c from the mitochondria. These two pathways may operate independently, yet it is known that some crosstalk occurs to regulate certain apoptotic events. Zhang et al. have identified a protein called bifunctional apoptosis regulator (BAR) that may be the molecular bridge between these two pathways. The authors determined that BAR binds to Bcl-2 and suppresses Bax-induced cell death. BAR also has a DED-like domain that binds to procaspase-8, and this interaction is necessary to suppress Fas-induced apoptosis. A procaspase-8-BAR-Bcl-2 complex could also be isolated from transfected cells. Further analysis of BAR should reveal how this protein potentially regulates two apoptotic signaling pathways.

Zhang, H., Xu, Q., Krajewski, S., Krajewski, M., Xie, Z., Fuess, S., Kitada, S., Pawlowski, K., Godsik, A., and Reed, J.C. (2000) BAR: An apoptosis regulator at the intersection of caspases and Bcl-2 family proteins. Proc. Natl. Acad. Sci. U.S.A. 97: 2597-2602. [Abstract] [Full Text]

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