USP11 regulates p53 stability by deubiquitinating p53

Ke, Jing; Dai, Congjie; Wu, Wenlin; Gao, Jinhua; Xia, Ai-juan; Liu, Guang-ping; Lv, Kaosheng; Wu, Chunlin

doi:10.1631/jzus.b1400180

Cited by 51 publications

(35 citation statements)

References 38 publications

(46 reference statements)

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“…In response to various stresses including DNA damage and oxidative stress, activation of p53 induces p21 protein expression by binding its promoter (31). A recent study revealed that USP11 deubiquitylates and stabilizes p53 (32). However, our results indicated that USP11 had no effect on p53.…”

Section: Discussioncontrasting

confidence: 72%

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

Deng

Yan

Zhou

et al. 2017

Preprint

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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 USP11 as a deubiquitylase of p21. In the nucleus, USP11 binds to p21, catalyzes the removal of polyubiquitin chains conjugated onto p21 and stabilizes not peer-reviewed)

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Section: Discussioncontrasting

confidence: 72%

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

Deng

Yan

Zhou

et al. 2017

Preprint

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“…USP11 binds to several substrates, mediating their stabilization and deubiquitination. USP11 interacts with and stabilizes p53 by promoting its deubiquitination [7]. The deubiquitinase activity of USP11 is involved in the regulation of BRCA2 in response to DNA damage, leading to increased survival of cancer cells [8].…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin-specific protease 11 serves as a marker of poor prognosis and promotes metastasis in hepatocellular carcinoma

Zhang

Xie

et al. 2018

Laboratory Investigation

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Ubiquitin-specific protease 11 (USP11) is a deubiquitinating enzyme that exerts its biological functions by regulating multiple signaling pathways such as p53, NF-κB, TGF-β, and Hippo. A large body of evidence supports a link between UPS11 and tumorigenesis. However, the clinical significance and biological function of USP11 in hepatocellular carcinoma (HCC) remains unclear. Here, USP11 expression was assessed by immunohistochemistry in a pilot series of 71 HCC clinical samples, and the association between USP11 expression and clinicopathological features and overall survival time was analyzed. The cytoplasmic expression rate of USP11 was higher in non-cancerous tissue than that in cancer tissue (36.6 vs. 12.7%, P = 0.001), whereas the nuclear expression rate of USP11 was lower in non-cancerous tissue (5.6 vs. 69.0%, P < 0.001). USP11 expression level was higher in tumor than that in non-tumor tissue (P < 0.001). Chi-square analysis of variances suggested that USP11 expression was associated with vascular invasion (P = 0.033), differentiation (P = 0.027), tumor number (P = 0.009), and recurrence (P = 0.036). USP11 expression was also associated with shorter overall survival time (P = 0.001) by log-rank test. Unconditional logistic regression analysis with multiple covariates indicated that high USP11 expression was associated with a 2.96-fold increase in the risk of death compared with low USP11 levels (P = 0.041) and acted as an independent predictor of overall survival. HCC patients with simultaneously high USP11 and alpha-fetoprotein expression had an adjusted 5-fold higher risk of all-cause-related death (P = 0.006). Moreover, in vitro and in vivo experiments confirmed that USP11 could promote the migration and invasion of HCC cell. Overall, we suggest that USP11 promotes HCC cell metastasis, and we provide the first evidence of the prognostic significance of USP11 expression in HCC, which suggests that USP11 is a promising therapeutic target for the treatment of HCC.

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“…They found also that USP24 deubiquitylates p53, activating the PUMA pathway, a regulator of DNA-damage-induced apoptosis ( Zhang L. et al, 2015 ). Similarly, it was found that USP11 deubiquitylates p53 in response to genotoxicity induced by etoposide ( Ke et al, 2014 ). Other DUBs are linked to the turn-over of important tumor suppressors and oncogenes.…”

Section: Regulation Of P53 C-myc and Other Oncogenes By Dubsmentioning

confidence: 93%

DUBbing Cancer: Deubiquitylating Enzymes Involved in Epigenetics, DNA Damage and the Cell Cycle As Therapeutic Targets

Pinto-Fernández

Kessler

2016

Front. Genet.

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Controlling cell proliferation is one of the hallmarks of cancer. A number of critical checkpoints ascertain progression through the different stages of the cell cycle, which can be aborted when perturbed, for instance by errors in DNA replication and repair. These molecular checkpoints are regulated by a number of proteins that need to be present at the right time and quantity. The ubiquitin system has emerged as a central player controlling the fate and function of such molecules such as cyclins, oncogenes and components of the DNA repair machinery. In particular, proteases that cleave ubiquitin chains, referred to as deubiquitylating enzymes (DUBs), have attracted recent attention due to their accessibility to modulation by small molecules. In this review, we describe recent evidence of the critical role of DUBs in aspects of cell cycle checkpoint control, associated DNA repair mechanisms and regulation of transcription, representing pathways altered in cancer. Therefore, DUBs involved in these processes emerge as potentially critical targets for the treatment of not only hematological, but potentially also solid tumors.

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USP11 regulates p53 stability by deubiquitinating p53

Cited by 51 publications

References 38 publications

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

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

Ubiquitin-specific protease 11 serves as a marker of poor prognosis and promotes metastasis in hepatocellular carcinoma

DUBbing Cancer: Deubiquitylating Enzymes Involved in Epigenetics, DNA Damage and the Cell Cycle As Therapeutic Targets

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