Full Text:   <2337>

Summary:  <1757>

CLC number: Q291

On-line Access: 2014-12-03

Received: 2014-06-30

Revision Accepted: 2014-11-11

Crosschecked: 2014-11-26

Cited: 10

Clicked: 4089

Citations:  Bibtex RefMan EndNote GB/T7714


Jia-ying KE


Chun-lin WU


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Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.12 P.1032-1038


USP11 regulates p53 stability by deubiquitinating p53*

Author(s):  Jia-ying Ke1,2, Cong-jie Dai1,2, Wen-lin Wu1,2, Jin-hua Gao3, Ai-juan Xia4, Guang-ping Liu5, Kao-sheng Lv6, Chun-lin Wu7

Affiliation(s):  1. College of Chemistry and Life Science, Quanzhou Normal University, Quanzhou 36200, China; more

Corresponding email(s):   kejiaying2003@163.com

Key Words:  p53, USP11, Deubiquitination, Stability

Jia-ying Ke, Cong-jie Dai, Wen-lin Wu, Jin-hua Gao, Ai-juan Xia, Guang-ping Liu, Kao-sheng Lv, Chun-lin Wu. USP11 regulates p53 stability by deubiquitinating p53[J]. Journal of Zhejiang University Science B, 2014, 15(12): 1032-1038.

@article{title="USP11 regulates p53 stability by deubiquitinating p53",
author="Jia-ying Ke, Cong-jie Dai, Wen-lin Wu, Jin-hua Gao, Ai-juan Xia, Guang-ping Liu, Kao-sheng Lv, Chun-lin Wu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T USP11 regulates p53 stability by deubiquitinating p53
%A Jia-ying Ke
%A Cong-jie Dai
%A Wen-lin Wu
%A Jin-hua Gao
%A Ai-juan Xia
%A Guang-ping Liu
%A Kao-sheng Lv
%A Chun-lin Wu
%J Journal of Zhejiang University SCIENCE B
%V 15
%N 12
%P 1032-1038
%@ 1673-1581
%D 2014
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1400180

T1 - USP11 regulates p53 stability by deubiquitinating p53
A1 - Jia-ying Ke
A1 - Cong-jie Dai
A1 - Wen-lin Wu
A1 - Jin-hua Gao
A1 - Ai-juan Xia
A1 - Guang-ping Liu
A1 - Kao-sheng Lv
A1 - Chun-lin Wu
J0 - Journal of Zhejiang University Science B
VL - 15
IS - 12
SP - 1032
EP - 1038
%@ 1673-1581
Y1 - 2014
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1400180

The p53 tumor suppressor protein coordinates the cellular responses to a broad range of cellular stresses, leading to DNA repair, cell cycle arrest or apoptosis. The stability of p53 is essential for its tumor suppressor function, which is tightly controlled by ubiquitin-dependent degradation primarily through its negative regulator murine double minute 2 (Mdm2). To better understand the regulation of p53, we tested the interaction between p53 and USP11 using co-immunoprecipitation. The results show that USP11, an ubiquitin-specific protease, forms specific complexes with p53 and stabilizes p53 by deubiquitinating it. Moreover, down-regulation of USP11 dramatically attenuated p53 induction in response to DNA damage stress. These findings reveal that USP11 is a novel regulator of p53, which is required for p53 activation in response to DNA damage.


深入研究p53的泛素化及稳定性的调控。 发现一个新的调控p53去泛素化的酶USP11,它可以通过与p53的结合去泛素化并稳定p53,从而揭示了一个新的p53去泛素化调控的机制。 通过免疫共沉淀发现p53可以与USP11结合(图1a),通过泛素化检测试验发现USP11可以去泛素化p53(图3a和3b),最后通过逆转录-聚合酶链式反应(RT-PCR)试验发现在DNA损伤后,USP11对p53转录活性的提高是非常重要的。 USP11可通过去泛素化p53来调控p53稳定性。

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Article Content


[1] Al-Salihi, M.A., Herhaus, L., Macartney, T., 2012. USP11 augments TGFβ signalling by deubiquitylating ALK5. Open Biol, 2(6):120063

[2] Bensaad, K., Tsuruta, A., Selak, M.A., 2006. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell, 126(1):107-120. 

[3] Brooks, C.L., Gu, W., 2006. p53 ubiquitination: Mdm2 and beyond. Mol Cell, 21(3):307-315. 

[4] Chen, D., Kon, N., Li, M., 2005. ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor. Cell, 121(7):1071-1083. 

[5] Cummins, J.M., Rago, C., Kohli, M., 2004. Tumour suppression: disruption of HAUSP gene stabilizes p53. Nature, 428(6982):1 p following 486

[6] Dornan, D., Wertz, I., Shimizu, H., 2004. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature, 429(6987):86-92. 

[7] Harris, S.L., Levine, A.J., 2005. The p53 pathway: positive and negative feedback loops. Oncogene, 24(17):2899-2908. 

[8] Haupt, Y., Maya, R., Kazaz, A., 1997. Mdm2 promotes the rapid degradation of p53. Nature, 387(6630):296-299. 

[9] Honda, R., Tanaka, H., Yasuda, H., 1997. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett, 420(1):25-27. 

[10] Ideguchi, H., Ueda, A., Tanaka, M., 2002. Structural and functional characterization of the USP11 deubiquitinating enzyme, which interacts with the RanGTP-associated protein RanBPM. Biochem J, 367(Pt 1):87-95. 

[11] Kruse, J.P., Gu, W., 2009. Modes of p53 regulation. Cell, 137(4):609-622. 

[12] Kubbutat, M.H., Jones, S.N., Vousden, K.H., 1997. Regulation of p53 stability by Mdm2. Nature, 387(6630):299-303. 

[13] Leng, R.P., Lin, Y., Ma, W., 2003. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell, 112(6):779-791. 

[14] Li, M., Chen, D., Shiloh, A., 2002. Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature, 416(6881):648-653. 

[15] Li, M., Brooks, C.L., Kon, N., 2004. A dynamic role of HAUSP in the p53-Mdm2 pathway. Mol Cell, 13(6):879-886. 

[16] Li, Y., Sun, X.X., Elferich, J., 2014. Monoubiquitination is critical for ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (Otub1) to suppress UbcH5 enzyme and stabilize p53 protein. J Biol Chem, 289(8):5097-5108. 

[17] Liu, J., Chung, H.J., Vogt, M., 2011. JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress. EMBO J, 30(5):846-858. 

[18] Liu, J., Zhang, C., Feng, Z., 2014. Tumor suppressor p53 and its gain-of-function mutants in cancer. Acta Biochim Biophys Sin, 46(3):170-179. 

[19] Luo, J., Lu, Z., Lu, X., 2013. OTUD5 regulates p53 stability by deubiquitinating p53. PLoS ONE, 8(10):e77682

[20] Madan, E., Gogna, R., Kuppusamy, P., 2012. TIGAR induces p53-mediated cell-cycle arrest by regulation of RB-E2F1 complex. Br J Cancer, 107(3):516-526. 

[21] Meulmeester, E., Pereg, Y., Shiloh, Y., 2005. ATM-mediated phosphorylations inhibit Mdmx/Mdm2 stabilization by HAUSP in favor of p53 activation. Cell Cycle, 4(9):1166-1170. 

[22] Michael, D., Oren, M., 2003. The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol, 13(1):49-58. 

[23] Nag, S., Qin, J., Srivenugopal, K.S., 2013. The MDM2-p53 pathway revisited. J Biomed Res, 27(4):254-271. 

[24] Riley, T., Sontag, E., Chen, P., 2008. Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol, 9(5):402-412. 

[25] Schoenfeld, A.R., Apgar, S., Dolios, G., 2004. BRCA2 is ubiquitinated in vivo and interacts with USP11, a deubiquitinating enzyme that exhibits prosurvival function in the cellular response to DNA damage. Mol Cell Biol, 24(17):7444-7455. 

[26] Sowa, M.E., Bennett, E.J., Gygi, S.P., 2009. Defining the human deubiquitinating enzyme interaction landscape. Cell, 138(2):389-403. 

[27] Sun, W., Tan, X., Shi, Y., 2010. USP11 negatively regulates TNFα-induced NF-κB activation by targeting on IκBα. Cell Signal, 22(3):386-394. 

[28] Sun, X.X., Dai, M.S., 2014. Deubiquitinating enzyme regulation of the p53 pathway: a lesson from Otub1. World J Biol Chem, 5(2):75-84. 

[29] Sun, X.X., Challagundla, K.B., Dai, M.S., 2012. Positive regulation of p53 stability and activity by the deubiquitinating enzyme Otubain 1. EMBO J, 31(3):576-592. 

[30] Thirunavukarasou, A., Singh, P., Govindarajalu, G., 2014. E3 ubiquitin ligase Cullin4B mediated polyubiquitination of p53 for its degradation. Mol Cell Biochem, 390(1-2):93-100. 

[31] Vogelstein, B., Lane, D., Levine, A.J., 2000. Surfing the p53 network. Nature, 408(6810):307-310. 

[32] Vousden, K.H., Prives, C., 2009. Blinded by the light: the growing complexity of p53. Cell, 137(3):413-431. 

[33] Wang, L., Zhang, S., Qu, G., 2013. Downregulation of ubiquitin E3 ligase TNF receptor-associated factor 7 leads to stabilization of p53 in breast cancer. Oncol Rep, 29(1):283-287. 

[34] Wiltshire, T.D., Lovejoy, C.A., Wang, T., 2010. Sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition identifies ubiquitin-specific peptidase 11 (USP11) as a regulator of DNA double-strand break repair. J Biol Chem, 285(19):14565-14571. 

[35] Won, K.Y., Lim, S.J., Kim, G.Y., 2012. Regulatory role of p53 in cancer metabolism via SCO2 and TIGAR in human breast cancer. Hum Pathol, 43(2):221-228. 

[36] Wu, H.C., Lin, Y.C., Liu, C.H., 2014. USP11 regulates PML stability to control Notch-induced malignancy in brain tumours. Nat Commun, 5:3214

[37] Yamaguchi, T., Kimura, J., Miki, Y., 2007. The deubiquitinating enzyme USP11 controls an IκB kinase α (IKKα)-p53 signaling pathway in response to tumor necrosis factor α (TNFα). J Biol Chem, 282(47):33943-33948. 

[38] Yuan, J., Luo, K., Zhang, L., 2010. USP10 regulates p53 localization and stability by deubiquitinating p53. Cell, 140(3):384-396. 

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