Reduced cyclin D1 ubiquitination in UVB-induced murine squamous cell carcinomas.
Ubiquitination of cyclin D1 signals for its proteosomal degradation. To assess the possibility that reduced cyclin D1 proteolysis is a putative mechanism for its accumulation during UVB-induced skin tumorigenesis, ubiquitination activity of cyclin D1 was assessed in UVB-induced murine SCCs. Cyclin D1 was rapidly ubiquitinated by control skin extract, whereas ubiquitination of cyclin D1 was significantly reduced in SCCs. Mutant cyclin D1, in which residues important for GSK3beta-mediated degradation of cyclin D1 are altered to non-phosphorylatable alanine, was not ubiquitinated. We also observed phosphorylation-dependent inactivation of GSK3beta in SCCs. Our results indicate reduced ubiquitination of cyclin D1 in UVB-induced murine SCCs and suggest that inactivation of GSK3beta-dependent cyclin D1 degradation pathway contributes to the accumulation of cyclin D1 in UVB-induced murine SCCs.
Kim
Arianna L
AL
Department of Dermatology, Columbia University College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Gautier
Jean
J
Bickers
David R
DR
Athar
Mohammad
M
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D008812:Mice, Hairless; D009097:Multienzyme Complexes / Q000378:metabolism; D009381:Neoplasms, Radiation-Induced / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D012878:Skin Neoplasms / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D014466:Ultraviolet Rays
D009097:Multienzyme Complexes; D025801:Ubiquitin; D019938:Cyclin D1; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex