Deubiquitylation and stabilization of p21 by USP11 is critical for cell-cycle progression and DNA damage responses

• DOI: 10.1073/pnas.1714938115
• Publication Date: 2018-04-17T15:03:29Z
• Authors: Tanggang Deng; Guobei Yan; Xin Song; Lin Xie; Yu Zhou; Jianglin Li; Xiaoxiao Hu; Zhen Li; Jun Hu; Yibin Zhang; Hui Zhang; Yang Sun; Peifu Feng; Dong Wei; Bin Hu; Jing Liu; Weihong Tan; Mao Ye
• Keywords: Cell Nucleus; Cyclin-Dependent Kinase Inhibitor p21; 0301 basic medicine; Cell Cycle; Ubiquitination; Apoptosis; Biological Sciences; 03 medical and health sciences; HEK293 Cells; A549 Cells; Proteolysis; Humans; Ubiquitin-Specific Proteases; DNA Damage; Signal Transduction

Significance Previous studies have demonstrated that p21 occupies a central position in cell-cycle regulation and DNA damage responses. As an unstable protein, the regulation of p21 stability has been extensively investigated over the past 20 years. Although p21 degradation by the ubiquitin-proteasome pathway has been well characterized, it is unclear whether ubiquitylated p21 can be recycled. Here, we identify USP11 as a deubiquitylase that directly removes p21 polyubiquitylation and stabilizes p21 protein, revealing that cellular p21 protein is finely regulated by a dynamic balance of USP11-mediated stabilization and proteasome-mediated degradation. Meanwhile, we also provide evidence that the USP11-p21 axis plays a crucial role in G1/S transition under physiological conditions and in regulating the balance between cytostasis and apoptosis.