Boo, a novel negative regulator of cell death, interacts with Apaf-1

In this report, we describe the cloning and characterization of Boo, a nove l anti-apoptotic member of the Bcl-2 family, The expression of Boo was high ly restricted to the ovary and epididymis implicating it in the control of ovarian atresia and sperm maturation, Boo contains the conserved BH1 and BH 2 domains, but lacks the BH3 motif, Like Bcl-2, Boo possesses a hydrophobic C-terminus and localizes to intracellular membranes, Boo also has an N-ter minal region with strong homology to the BH4 domain found to be important f or the function of some anti-apoptotic Bcl-2 homologues. Chromosomal locali zation analysis assigned Boo to murine chromosome 9 at band do, Boo inhibit s apoptosis, homodimerizes or heterodimerizes with some death-promoting and -suppressing Bcl-2 family members, More importantly, Boo interacts with Ap af-1 and forms a multimeric protein complex with Apaf-1 and caspase-9, Bak and Bik, two pro-apoptotic homologues disrupt the association of Boo and Ap af-1, Furthermore, Boo binds to three distinct regions of Apaf-1. These res ults demonstrate the evolutionarily conserved nature of the mechanisms of a poptosis, Like Ced-9, the mammalian homologues Boo and Bcl-x(L) interact wi th the human counterpart of Ced-4, Apaf-1, and thereby regulate apoptosis.