Livin Prevents Dyin' (By Apoptosis)

The inhibitor of apoptosis (IAP) protein family continues to grow. Kasof and Gomes have characterized a new IAP termed "Livin" that protects cells from TNF-α-mediated apoptosis. Livin, which has one baculovirus IAP repeat (BIR) domain and a RING domain, was expressed in cells normally associated with rapid growth: placental tissue, fetal brain, and some cancer cell lines. Transfection of Livin, as compared with the related IAP survivin, inhibited apoptosis to a greater degree in HeLa cells that co-expressed individual components of the TNF-α signaling pathway. (Perhaps this indicates that Livin is better than survivin-sage Maslovian advice from the world of cell biology.) Further transfection studies indicated that the Livin BIR domain was responsible for mediating the anti-apoptotic effect. Livin bound to procaspase-9 and partially prevented the proteolytic cleavage and activation of caspase-9 in TNF-α-treated cells. Although Livin also associated with active caspase-3 and caspase-7 in vitro, these investigators did not test whether Livin could inhibit their activation from their procaspase forms. Expression of different Livin truncation mutants suggested that the COOH-terminal RING domain is necessary for the proper subcellular localization of Livin. Additionally, the expression antisense Livin cDNA in cells correlated with increased apotosis. Thus, these data suggest that Livin is a physiologically important regulator of caspase activation and apoptosis. G. M. Kasof , B. C. Gomes, Livin, a novel inhibitor of apoptosis protein family member. J. Biol. Chem. 276 : 3238-3246 (2001). [Abstract] [Full Text]