Inhibition of homologue of Slimb (HOS) function sensitizes human melanoma cells for apoptosis

Homologue of Slimb (HOS)/beta-transducin repeats containing proteins up-reg ulate nuclear factor kappa B activity by targeting its inhibitor (I kappa B ) for ubiquitination and subsequent degradation. We investigated whether in hibition of HOS function may modulate apoptosis in human melanoma cells. Fo rced expression of the dominant negative HOSDelta F construct inhibited I k appa B degradation and led to sensitization of melanoma cells to apoptosis induced by tumor necrosis factor alpha with cycloheximide, as well as by ci splatin and ionizing and UV irradiation. These data indicate that HOS plays an important role in controlling the I kappa B-dependent apoptotic pathway s in human melanoma.