title: Multistep and multitask Bax activation.
abstract: Bax is a pro-apoptotic protein allowing apoptosis to occur through the intrinsic, damage-induced pathway, and amplifying that one occurring via the extrinsic, receptor mediated pathway. Bax is present in viable cells and activated by pro-apoptotic stimuli. Activation implies structural changes, consisting of exposure of the N terminus and hydrophobic domains; changes in localization, consisting in migration from cytosol to mitochondria and endoplasmic reticulum membranes; changes in the aggregation status, from monomer to dimer and multimer. Bax has multiple critical domains, namely the N terminus exposed after activation; two hydrophobic stretches exposed for membrane anchorage; two reactive cysteines allowing multimerization; the BH3 domain for interactions with the Bcl-2 family members; alpha helix 1 for t-Bid interaction. Bax has also multiple functions: it releases different mitochondrial factors such as cytochrome c, SMAC/diablo; it regulates mitochondrial fission, the mitochondrial permeability transition pore; it promotes Ca(2+) leakage through ER membrane. Altogether, Bax activation is a complex multi-step phenomenon. Here, we analyze these events as logically separable or alternative steps, attempting to assess their role, timing and reciprocal relation.
authors: Dipartimento di Biologia, Universita' di Roma Tor Vergata, Via della Ricerca Scientifica, I-00133 Rome, Italy. ghibelli@uniroma2.it
authors: Lina
authors: L
authors: Ghibelli
authors: Marc
authors: M
authors: Diederich
mesh_terms: D017209:Apoptosis; D003600:Cytosol / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000737:chemistry; D008928:Mitochondria / Q000737:chemistry* / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D051028:bcl-2-Associated X Protein / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D051028:bcl-2-Associated X Protein