Involvement of the N-terminus of Bax in its intracellular localization and function

• Published in: FEBS letters 2002-02, Vol.512 (1), p.95-100
• Main Authors: Cartron, P.-F., Moreau, C., Oliver, L., Mayat, E., Meflah, K., Vallette, F.M.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Apoptosis; ART, apoptotic regulation of targeting; Bax; Bax, Baxα; bcl-2-Associated X Protein; BdGBM, Bax-deficient glioblastoma multiforme; BH3 Interacting Domain Death Agonist Protein; Carrier Proteins - metabolism; Cell Compartmentation; Conformation; CT, COOH-terminus of human Bax; Cytosol - metabolism; doxo, doxorubicin; Intracellular Membranes - metabolism; Mitochondria, Liver - metabolism; Molecular Sequence Data; Mutagenesis; Mutation; NT, NH2-terminus of human Bax; Proline - genetics; Proline - metabolism; Protein Binding; Protein Structure, Tertiary; Protein Transport; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(02)02227-5

We have identified, using site-directed mutagenesis, a proline located at position 13 of Baxα (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.