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Inhibition of Homologue of Slimb (HOS) Function Sensitizes Human Melanoma Cells for Apoptosis¹

Department of Radiation Medicine, Lombardi Cancer Center, Georgetown University Medical Center, Washington, D.C. 20007 [V. A. S., A. D.], and The Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029 [Z. R., S. Y. F.]

Homologue of Slimb (HOS)/-transducin repeats containing proteins up-regulate nuclear factor B activity by targeting its inhibitor (IB) for ubiquitination and subsequent degradation. We investigated whether inhibition of HOS function may modulate apoptosis in human melanoma cells. Forced expression of the dominant negative HOS^F construct inhibited IB degradation and led to sensitization of melanoma cells to apoptosis induced by tumor necrosis factor with cycloheximide, as well as by cisplatin and ionizing and UV irradiation. These data indicate that HOS plays an important role in controlling the IB-dependent apoptotic pathways in human melanoma.

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