Combinatorial interaction of human bcl-2 related proteins: mapping of regions important for bcl-2/bcl-x-s interaction.

Human bcl-2 family of genes including bcl-2, bcl-x-l, bcl-x-s, and bax has been shown to be functionally involved in apoptosis. We applied a yeast two-hybrid system to demonstrate that bcl-2, bcl-x-l, bcl-x-s, and bax proteins can interact with each other directly. All bcl-2 family members except bax were shown to be capable of homo-interactions. By using deletion and point mutations, the interaction domains for bcl-2 and bcl-x-s were elucidated. The BH1 domain and the membrane anchoring region at the C-terminal half of the bcl-2 protein are required for its interaction with bcl-x-s. On the other hand, the N-terminal region consisting of codons 24 to 78 of bcl-x-s interacts with bcl-2.