title: Bax-independent inhibition of apoptosis by Bcl-XL.
abstract: The Bcl-2-related protein, Bcl-XL, has been shown to block apoptosis induced by a variety of stimuli and to be a stronger protector against apoptosis than Bcl-2 under certain circumstances. Using site-specific mutagenesis, we show here that the amino-acid residues critical for protection of cells by Bcl-XL against Sindbis virus-induced apoptosis are clustered within the Bcl-2-homology regions 1 and 2 (BH1 and BH2 regions). The residues necessary for Bcl-XL function are not identical to those required for Bcl-2 function. Although it has been suggested that heterodimerization between Bcl-XL and Bax is essential for the anti-death activity of Bcl-XL (refs 7,8), our results suggest that the interaction with Bax is not required for Bcl-XL to exert its death-repressing activity. Specific mutations that disrupt the ability of Bcl-XL to interact with Bax or Bak still preserve 70-80% of the anti-death activity of wild-type Bcl-XL.
authors.affiliation: Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland 21287-7681, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Cheng
authors.forename: B
authors.initials: B
authors.lastname: Levine
authors.forename: L H
authors.initials: LH
authors.lastname: Boise
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson
authors.forename: J M
authors.initials: JM
authors.lastname: Hardwick
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001665:Binding Sites; D001704:Biopolymers; D002460:Cell Line; D005822:Genetic Vectors; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D012845:Sindbis Virus / Q000502:physiology; D014162:Transfection; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
chemical_list: C494826:BAX protein, human; C494811:BCL2L1 protein, human; D001704:Biopolymers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein