Transmembrane domain of Bcl-2 is required for inhibition of ceramide synthesis, but not cytochrome c release in the pathway of inostamycin-induced apoptosis

摘要: Bcl-2 protein plays important roles in the regulation of apoptosis. However, exact mechanism by which blocks apoptosis is still unclear. In present study, we found that overexpression human small cell lung carcinoma Ms-1 cells inhibited not only release cytochrome c from mitochondria into cytosol but also de novo ceramide synthesis induced inostamycin, a phosphatidylinositol turnover inhibitor. To investigate correlation between structure and its inhibitory function inostamycin-induced apoptosis, stably overexpress domain-deletional mutants were established. Transmembrane domain-deleted failed to inhibit synthesis, whereas it release, indicating anchoring membrane was requirement for effect on release. Thus, deletion mutant tarnsmembrane domain can suppress inhibiting downstream event pathway We BH3 BH4 domains necessary inhibition BH1 or BH2 did affect apoptotic events.