Bcl-w(edding) with mitochondria.
Bcl-2-family members (Bcl-2, Bax, Bcl-w and Bcl-x(L)) are crucial integrators of signals for cell survival and death; the pro- or antiapoptotic activities of these proteins are regulated by their subcellular localization. Bcl-2 directly inserts into the membranes, where it acts; however, Bax requires a stimulus-dependent translocation from an inactive cytosolic to an active membrane-inserted state. Recently, a novel mechanism is described for the survival factor Bcl-w, which is active while weakly associated with mitochondria. In apoptotic cells, a BH3-only protein neutralizes the survival activity of Bcl-w by binding to its "hydrophobic pockets", thereby releasing its C-terminal domain and allowing its insertion into the membrane. Here, we discuss the importance of this finding for a better understanding of the action mode of Bcl-w and other Bcl-2-family members.
Kaufmann
Thomas
T
Institute of Molecular Medicine and Cell Research, Zentrale Klinische Forschung (ZKF), Albert-Ludwigs-University Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany
Schinzel
Anna
A
Borner
Christoph
C
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2