title: UV Induces p21 rapid turnover independently of ubiquitin and Skp2.
abstract: It was previously reported that low doses, but not high doses, of UV trigger the Skp2-mediated proteasomal degradation of the cyclin-dependent kinase inhibitor p21 in mammalian cells. Here we show that both UV-C and UV-B lead to decrease of p21 protein, but not mRNA, level in a dose-dependent fashion in all of six human cell lines and five mouse cell lines tested. Also, high doses of UV reduce the half-life of p21. High doses, but not low doses, of UV induced p21 degradation in both skp2-proficient and -deficient murine embryonic fibroblast cells. UV-induced p21 reduction was rescued by proteasome inhibitors in all human and mouse cell lines tested. Neither a caspase inhibitor nor small interfering RNA against skp2 had an effect on the UV-induced p21 decrease, suggesting that this p21 degradation pathway may not involve caspases, or Skp2. Finally, UV did not induce p21 ubiquitination but still induced its degradation when the E1-activating enzyme was inactivated in an E1 temperature-sensitive mouse embryonic fibroblast cell line. Altogether, these results demonstrate that UV induces p21 degradation through an Skp2 and ubiquitin-independent pathway.
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, Oregon 97239, USA.
authors.forename: Hunjoo
authors.initials: H
authors.lastname: Lee
authors.forename: Shelya X
authors.initials: SX
authors.lastname: Zeng
authors.forename: Hua
authors.initials: H
authors.lastname: Lu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D044786:S-Phase Kinase-Associated Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D016283:Proto-Oncogene Proteins p21(ras)