Members of the Bcl-2 protein family contains 1 to 4 bcl-2 homology domains (BH1-4), and in some cases, C-terminal hydrophobic regions that promote membrane binding. Bcl-2 is the prototypic anti-apoptotic gene that encodes two protein products, Bcl-2a and Bcl-2b, which differ at their C-terminal hydrophobic regions that localize them to the mitochrondrial membrane. Bcl-2 inhibition of apoptosis is modulated by homodimerization or heterodimirezetion with Bax, Bad and Beclin. Like Bcl-2, Bcl-xL inhibits cell death. Bcl-x proteins include, bcl-xL and bcl-xS, which arise from alternate 5' splice sites located within the first coding exon of the bcl-x gene. Bcl-xL is 233 aa, and is similar in size and structure to Bcl-2. The bcl-xS polypeptide shows a deletion of 63 aa, which consist of the region of Bcl-xL with the highest degree of amino acid identity to Bcl-2. Bcl-xS inhibits Bcl-2 mediated cell survival. Anti-apoptotic functions of Bcl-2 and Bcl-x are regulated through interactions with Bax, Bak, Bad, Bid, Bim, and Bik. Bax contains the conserved BH1 and BH2 domains, which allow for its homodimerization or heterodimerization with Bcl-2. The ratio of Bax homodimers to Bax/Bcl-2 heterodimers is an apoptotic checkpoint. Bad contains BH1 and BH2 domains, and dimerizes with Bcl-xL and Bcl-2. Bid contains a BH3 domain, but does not contain other Bcl-2 family domains. Caspase-8 cleavage of Bid produces a 15 kDa C-terminal fragment and a 6.5 kDa N-terminal fragment. The C-terminal fragment translocates to the mitochondria and promotes the release of cytochrome C during apoptosis.