title: The alpha-5 helix of Bax is sensitive to ubiquitin-dependent degradation.
abstract: The pro-apoptotic protein Bax is instable in many cancer cells but the mechanism of Bax degradation remains unclear. Four different lengths of deductive Bax degradation sensitive (BDS) sequences within BH3-BH1 region, BDS-1 (Bax 67-124), BDS-3 (Bax 74-107), BDS-5 (Bax 67-107), and BDS-7 (Bax 74-124), were tested for the susceptibility to ubiquitin-dependent degradation. Both BDS-1 and BDS-7 which contain the alpha5 helix, a putative pore-forming domain of Bax, are sensitive to proteasome-dependent degradation and ubiquitin-conjugation. The Bax alpha5-deletion mutant (Bax-Deltaalpha5) was stable and also maintained its apoptosis-inducing ability. Deletion of helices alpha1 and part of alpha2 (Bax-Delta1-66) or helices alpha3 and alpha4 (Bax-Deltaalpha3,4) did not affect the sensitivity to degradation. However, Bax-Delta1-66 mutant was not able to induce apoptosis. Thus, we propose that the alpha5 helix of Bax is sensitive to ubiquitin-dependent degradation. Moreover, Bax mutant retains its pro-apoptosis ability when the alpha5 helix is deleted.
authors.affiliation: Centre for Haematology, Institute of Cell and Molecular Science, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Feng-Ting
authors.initials: FT
authors.lastname: Liu
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Newland
authors.forename: Li
authors.initials: L
authors.lastname: Jia
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary / Q000235:genetics; D017384:Sequence Deletion; D025801:Ubiquitin / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; D025801:Ubiquitin; D051028:bcl-2-Associated X Protein; D046988:Proteasome Endopeptidase Complex