Inhibition of homologue of Slimb (HOS) function sensitizes human melanoma cells for apoptosis.
Homologue of Slimb (HOS)/beta-transducin repeats containing proteins up-regulate nuclear factor kappaB activity by targeting its inhibitor (IkappaB) 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 HOSdeltaF construct inhibited IkappaB degradation and led to sensitization of melanoma cells to apoptosis induced by tumor necrosis factor alpha with cycloheximide, as well as by cisplatin and ionizing and UV irradiation. These data indicate that HOS plays an important role in controlling the IkappaB-dependent apoptotic pathways in human melanoma.
Soldatenkov
V A
VA
Department of Radiation Medicine, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
Dritschilo
A
A
Ronai
Z
Z
Fuchs
S Y
SY
D017209:Apoptosis; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D002945:Cisplatin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000502:physiology; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins
C495270:CTNNB1 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C471645:FBXW11 protein, human; D016328:NF-kappa B; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins; D003513:Cycloheximide; D044767:Ubiquitin-Protein Ligases; D002945:Cisplatin