title: Involvement of the N-terminus of Bax in its intracellular localization and function.
abstract: We have identified, using site-directed mutagenesis, a proline located at position 13 of Baxalpha (Bax) as crucial for the maintenance of its cytosolic conformation. The substitution of this proline by a valine results in a strong binding of Bax to mitochondria and to conformational changes monitored by a decreased sensitivity of Bax to mild proteolysis and the enhancement of its oligomerization state. Deletion of the C-terminus of Bax does not modify its intracellular localization. On the other hand, the pro-apoptotic activity of Bax is enhanced by a deletion of the C-terminus in the absence of the N-terminus but is decreased in its presence. These results suggest that both extremities functionally interact to control the activity but not the subcellular localization of Bax.
authors.affiliation: INSERM U419, IFR 26, 9 quai MONCOUSU, 44035 Cedex, Nantes, France.
authors.forename: P-F
authors.initials: PF
authors.lastname: Cartron
authors.forename: C
authors.initials: C
authors.lastname: Moreau
authors.forename: L
authors.initials: L
authors.lastname: Oliver
authors.forename: E
authors.initials: E
authors.lastname: Mayat
authors.forename: K
authors.initials: K
authors.lastname: Meflah
authors.forename: F M
authors.initials: FM
authors.lastname: Vallette
mesh_terms: D000595:Amino Acid Sequence; D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins / Q000378:metabolism; D002451:Cell Compartmentation; D003600:Cytosol / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011392:Proline / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D002352:Carrier Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D011392:Proline