The pro-apoptotic protein Bax is instable in many cancer cells but the mechanism of Bax degradation remains unclear. Four different lengths of deductive Bax degradation sensitive (BDS) sequences within BH3-BH1 region, BDS-1 (Bax 67-124), BDS-3 (Bax 74-107), BDS-5 (Bax 67-107), and BDS-7 (Bax 74-124), were tested for the susceptibility to ubiquitin-dependent degradation. Both BDS-1 and BDS-7 which contain the alpha5 helix, a putative pore-forming domain of Bax, are sensitive to proteasome-dependent degradation and ubiquitin-conjugation. The Bax alpha5-deletion mutant (Bax-Deltaalpha5) was stable and also maintained its apoptosis-inducing ability. Deletion of helices alpha1 and part of alpha2 (Bax-Delta1-66) or helices alpha3 and alpha4 (Bax-Deltaalpha3,4) did not affect the sensitivity to degradation. However, Bax-Delta1-66 mutant was not able to induce apoptosis. Thus, we propose that the alpha5 helix of Bax is sensitive to ubiquitin-dependent degradation. Moreover, Bax mutant retains its pro-apoptosis ability when the alpha5 helix is deleted.