Identification of a novel regulatory domain in Bcl-X(L) and Bcl-2.

Chang BS, Minn AJ, Muchmore SW, Fesik SW, Thompson CB
EMBO J. 1997 16 (5): 968-77

PMID: 9118958 · PMCID: PMC1169697 · DOI:10.1093/emboj/16.5.968

Bcl-X(L), a member of the Bcl-2 family, can inhibit many forms of programed cell death. The three-dimensional structure of Bcl-X(L) identified a 60 amino acid loop lacking defined structure. Although amino acid sequence within this region is not conserved among Bcl-2 family members, structural modeling suggested that Bcl-2 also contains a large unstructured region. Compared with the full-length protein, loop deletion mutants of Bcl-X(L) and Bcl-2 displayed an enhanced ability to inhibit apoptosis. Despite enhanced function, the deletion mutants did not have significant alterations in the ability to bind pro-apoptotic proteins such as Bax. The loop deletion mutant of Bcl-2 also displayed a qualitative difference in its ability to inhibit apoptosis. Full-length Bcl-2 was unable to prevent anti-IgM-induced cell death of the immature B cell line WEHI-231. In contrast, the Bcl-2 deletion mutant protected WEHI-231 cells from death. Substantial differences were observed in the ability of WEHI-231 cells to phosphorylate the deletion mutant of Bcl-2 compared with full-length Bcl-2. Bcl-2 phosphorylation was found to be dependent on the presence of an intact loop domain. These results suggest that the loop domain in Bcl-X(L) and Bcl-2 can suppress the anti-apoptotic function of these genes and may be a target for regulatory post-translational modifications.

MeSH Terms (24)

Amino Acid Sequence Animals Apoptosis B-Lymphocytes bcl-2-Associated X Protein bcl-X Protein Blotting, Western Cells, Cultured Cell Survival Clone Cells Dimerization Flow Cytometry Gene Expression Humans Mice Molecular Sequence Data Mutation Phosphorylation Precipitin Tests Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Sequence Deletion Sequence Homology, Amino Acid Transfection

Connections (1)

This publication is referenced by other Labnodes entities: