RT Journal Article SR Electronic T1 Deubiquitylation and stabilization of p21 by USP11 is critical for cell cycle progression and DNA damage responses JF bioRxiv FD Cold Spring Harbor Laboratory SP 172999 DO 10.1101/172999 A1 Tanggang Deng A1 Guobei Yan A1 Yu Zhou A1 Xiaoxiao Hu A1 Jianglin Li A1 Jun Hu A1 Hui Zhang A1 Peifu Feng A1 Xunan Sheng A1 Jieying Chen A1 Hongchang Ma A1 Yang Sun A1 Dong Wei A1 Bin Hu A1 Jing Liu A1 Weihong Tan A1 Mao Ye YR 2017 UL http://biorxiv.org/content/early/2017/08/07/172999.abstract AB p21WAF1/CIP1 is a broad-acting cyclin-dependent kinase inhibitor. Its stability is essential for proper cell cycle progression and cell fate decision. Ubiquitylation by the multiple E3 ubiquitin ligases complex is the major regulatory mechanism of p21, which induces p21 degradation. However, it is unclear whether ubiquitylated p21 can be recycled. In this study, we report that USP11 stabilized p21 by removing the polyubiquitin chains conjugated onto p21. Loss of USP11 promoted p21 degradation and induced the G1/S transition in unperturbed cells. Furthermore, the p21 accumulation mediated by DNA damage was completely abolished in cells depleted of USP11, resulting in the abrogation of the G2 checkpoint. Functionally, the USP11-mediated stabilization of p21 inhibited cell proliferation and tumorigenesis in vivo. These findings reveal an important mechanism by which p21 can be stabilized by direct deubiquitylation and pinpoint a critical role of USP11-p21 axis in regulating cell cycle progression and DNA damage responses.