UV Induces p21 Rapid Turnover Independently of Ubiquitin and Skp2

Hunjoo Lee,Shelya X Zeng,Hua Lu

doi:10.1074/jbc.m605366200

Hunjoo Lee, Shelya X Zeng + Show 1 more

Open Access

https://doi.org/10.1074/jbc.m605366200

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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.

Highlights

The tight cell cycle control is executed through the concerted efforts of cyclin-dependent kinases and their cellular inhibitors [1]
The reduction of the p21 level by high doses of UV was due to the decrease of p21 stability, but not the change of its mRNA, as this reduction was rescued by the proteasome inhibitor MG132, and again the p21 mRNA level was induced by high doses of UV (Fig. 1B)
These results indicate that UV-C and UV-B can reduce p21 protein, but not mRNA, levels independently of p53 activity in RPE cells

Summary

Introduction

The tight cell cycle control is executed through the concerted efforts of cyclin-dependent kinases and their cellular inhibitors [1]. The UV-induced reduction of p21 in this cell line was dose-dependent, as the protein level of p21 was inversely proportional to the dose of UV used for irradiation (Fig. 1, B and C).

Results

Conclusion