去泛素化酶OTUD1在肿瘤中的研究进展

孙利英; 柯少波; 刘奕; 黄志群; 陈永顺

doi:10.14188/j.1671-8852.2024.0205

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去泛素化酶OTUD1在肿瘤中的研究进展

肿瘤学研究 | 更新时间：2026-11-05

- 去泛素化酶OTUD1在肿瘤中的研究进展
- Research progress on deubiquitinase OTUD1 in cancer
- 武汉大学学报（医学版） 2025年46卷第9期页码：1161-1167
- 作者机构：
  
  1.武汉大学人民医院肿瘤中心湖北武汉 430060
  2.南华大学衡阳医学院基础医学院细胞生物学与遗传学系湖南衡阳 421001
  3.武汉大学人民医院耳鼻咽喉⁃头颈外科中心湖北武汉 430060
- 作者简介：
  
  孙利英，女，1995—，医学博士生，主要从事消化道肿瘤的研究，E‐mail：sunlyoo111@163.com
  陈永顺，男，1976—，医学博士，教授，博士生导师，主要从事消化道肿瘤的研究，E‐mail：yongshun2007@163.com
- 基金信息：
  
  湖北省中央引导地方科技发展专项(2020ZYYD006);湖北省自然科学基金项目(2023AFB711);湖南省自然科学基金项目(2024JJ6379)
- DOI：10.14188/j.1671-8852.2024.0205
  中图分类号： R730.2
- 收稿：2024-03-25，
  
  纸质出版：2025-09-26
- 稿件说明：
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孙利英,柯少波,刘奕等.去泛素化酶OTUD1在肿瘤中的研究进展[J].武汉大学学报（医学版）,2025,46(09):1161-1167.

SUN Liying,KE Shaobo,LIU Yi,et al.Research progress on deubiquitinase OTUD1 in cancer[J].Medical Journal of Wuhan University,2025,46(09):1161-1167.
孙利英,柯少波,刘奕等.去泛素化酶OTUD1在肿瘤中的研究进展[J].武汉大学学报（医学版）,2025,46(09):1161-1167. DOI： 10.14188/j.1671-8852.2024.0205.

SUN Liying,KE Shaobo,LIU Yi,et al.Research progress on deubiquitinase OTUD1 in cancer[J].Medical Journal of Wuhan University,2025,46(09):1161-1167. DOI： 10.14188/j.1671-8852.2024.0205.

摘要

泛素⁃蛋白酶体系统是体内主要的蛋白质降解途径。OTU去泛素酶1（OTUD1）是一种功能性的半胱氨酸蛋白酶，属于卵巢肿瘤蛋白酶家族。OTUD1在多种信号通路中通过去泛素化关键蛋白，对机体的病理和生理过程产生广泛影响。本文综述了OTUD1在恶性肿瘤中的作用及其参与的分子机制，探讨了将OTUD1作为新的治疗靶标的潜力，旨在为癌症治疗策略的开发提供理论基础和新的视角。

Abstract

The ubiquitin⁃proteasome system is the primary pathway for protein degradation within the body. OTU deubiquitinase 1 (OTUD1) is a functional cysteine protease and a member of the ovarian tumor protease family. OTUD1 plays a broad role in both pathological and physiological processes by deubiquitinating key proteins in various signaling pathways. This article reviews the role of OTUD1 in malignant tumors and its involvement in molecular mechanisms within related pathways

exploring the potential of OTUD1 as a new therapeutic target. This review aims to provide a theoretical basis and a new perspective for the development of cancer treatment strategies.

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references

ZHENG N , SHABEK N . Ubiquitin ligases: Structure, function, and regulation [J ] . Annu Rev Biochem , 2017 , 86 : 129 ⁃ 157 .

KWON Y T , CIECHANOVER A . The ubiquitin code in the ubiquitin⁃proteasome system and autophagy [J ] . Trends Biochem Sci , 2017 , 42 ( 11 ): 873 ⁃ 886 .

CLAGUE M J , URBÉ S , KOMANDER D . Breaking the chains: Deubiquitylating enzyme specificity begets function [J ] . Nat Rev Mol Cell Biol , 2019 , 20 ( 6 ): 338 ⁃ 352 .

MAKAROVA K S , ARAVIND L , KOONIN E V . A novel superfamily of predicted cysteine proteases from eukaryotes, viruses and Chlamydia pneumoniae [J ] . Trends Biochem Sci , 2000 , 25 ( 2 ): 50 ⁃ 52 .

DU J , FU L , SUI Y , et al . The function and regulation of OTU deubiquitinases [J ] . Front Med , 2020 , 14 ( 5 ): 542 ⁃ 563 .

OIKAWA D , SHIMIZU K , TOKUNAGA F . Pleiotropic roles of a KEAP1⁃associated deubiquitinase, OTUD1 [J ] . Antioxidants (Basel) , 2023 , 12 ( 2 ): 350 .

MEVISSEN T E , HOSPENTHAL M K , GEURINK P P , et al . OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis [J ] . Cell , 2013 , 154 ( 1 ): 169 ⁃ 184 .

CARNEIRO A P , REIS C F , MORARI E C , et al . A putative OTU domain⁃containing protein 1 deubiquitinating enzyme is differentially expressed in thyroid cancer and identifies less⁃aggressive tumours [J ] . Br J Cancer , 2014 , 111 ( 3 ): 551 ⁃ 558 .

ZHOU T , WU Y , QIAN D , et al . OTUD1 chemosensitizes triple⁃negative breast cancer to doxorubicin by modulating P16 expression [J ] . Pathol Res Pract , 2023 , 247 : 154571 .

ZHANG Z , FAN Y , XIE F , et al . Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7 [J ] . Nat Commun , 2017 , 8 ( 1 ): 2116 .

YAO F , ZHOU Z , KIM J , et al . SKP2⁃ and OTUD1⁃regulated non⁃proteolytic ubiquitination of YAP promotes YAP nuclear localization and activity [J ] . Nat Commun , 2018 , 9 ( 1 ): 2269 .

DENG J , HOU G , FANG Z , et al . Distinct expression and prognostic value of OTU domain⁃containing proteins in non⁃small⁃cell lung cancer [J ] . Oncol Lett , 2019 , 18 ( 5 ): 5417 ⁃ 5427 .

MA X , WANG L , SHI G , et al . The deubiquitinase OTUD1 inhibits non⁃small cell lung cancer progression by deubiquitinating and stabilizing KLF4 [J ] . Thorac Cancer , 2022 , 13 ( 5 ): 761 ⁃ 770 .

LIU H , ZHONG L , LU Y , et al . Deubiquitylase OTUD1 confers Erlotinib sensitivity in non⁃small cell lung cancer through inhibition of nuclear translocation of YAP1 [J ] . Cell Death Discov , 2022 , 8 ( 1 ): 403 .

ZHANG Q , LI J , CHEN Z , et al . VE⁃822 upregulates the deubiquitinase OTUD1 to stabilize FHL1 to inhibit the progression of lung adenocarcinoma [J ] . Cell Oncol (Dordr) , 2023 , 46 ( 4 ): 1001 ⁃ 1014 .

LUO Q , WU X , ZHAO P , et al . OTUD1 activates caspase⁃independent and caspase⁃dependent apoptosis by promoting AIF nuclear translocation and MCL1 degradation [J ] . Adv Sci (Weinh) , 2021 , 8 ( 8 ): 2002874 .

GRATTAROLA M , CUCCI M A , ROETTO A , et al . Post⁃translational down⁃regulation of Nrf2 and YAP proteins, by targeting deubiquitinases, reduces growth and chemoresistance in pancreatic cancer cells [J ] . Free Radic Biol Med , 2021 , 174 : 202 ⁃ 210 .

SONG J , LIU T , YIN Y , et al . The deubiquitinase OTUD1 enhances iron transport and potentiates host antitumor immunity [J ] . EMBO Rep , 2021 , 22 ( 2 ): e51162 .

LI J J , WANG J H , TIAN T , et al . The liver microenvironment orchestrates FGL1⁃mediated immune escape and progression of metastatic colorectal cancer [J ] . Nat Commun , 2023 , 14 ( 1 ): 6690 .

LIU W , YAN B , YU H , et al . OTUD1 stabilizes PTEN to inhibit the PI3K/AKT and TNF⁃alpha/NF⁃kappaB signaling pathways and sensitize ccRCC to TKIs [J ] . Int J Biol Sci , 2022 , 18 ( 4 ): 1401 ⁃ 1414 .

WOO S M , SEO S U , MIN K J , et al . Melatonin induces apoptotic cell death through Bim stabilization by Sp1⁃mediated OTUD1 upregulation [J ] . J Pineal Res , 2022 , 72 ( 1 ): e12781 .

CHEN Y , QIANG Y , FAN J , et al . Aggresome formation promotes ASK1/JNK signaling activation and stemness maintenance in ovarian cancer [J ] . Nat Commun , 2024 , 15 ( 1 ): 1321 .

VDOVIN A , JELINEK T , ZIHALA D , et al . The deubiquitinase OTUD1 regulates immunoglobulin production and proteasome inhibitor sensitivity in multiple myeloma [J ] . Nat Commun , 2022 , 13 ( 1 ): 6820 .

FAN G , WANG F , CHEN Y , et al . The deubiquitinase OTUD1 noncanonically suppresses Akt activation through its N⁃terminal intrinsically disordered region [J ] . Cell Rep , 2023 , 42 ( 1 ): 111916 .

PIAO S , PEI H Z , HUANG B , et al . Ovarian tumor domain⁃containing protein 1 deubiquitinates and stabilizes p53 [J ] . Cell Signal , 2017 , 33 : 22 ⁃ 29 .

SIEGEL R L , MILLER K D , FUCHS H E , et al . Cancer statistics, 2022 [J ] . CA Cancer J Clin , 2022 , 72 ( 1 ): 7 ⁃ 33 .

NOLAN E , LINDEMAN G J , VISVADER J E . Deciphering breast cancer: From biology to the clinic [J ] . Cell , 2023 , 186 ( 8 ): 1708 ⁃ 1728 .

GERSTBERGER S , JIANG Q , GANESH K . Metastasis [J ] . Cell , 2023 , 186 ( 8 ): 1564 ⁃ 1579 .

YU F X , ZHAO B , GUAN K L . Hippo pathway in organ size control, tissue homeostasis, and cancer [J ] . Cell , 2015 , 163 ( 4 ): 811 ⁃ 828 .

WANG L , CHOI K , SU T , et al . Multiphase coalescence mediates Hippo pathway activation [J ] . Cell , 2022 , 185 ( 23 ): 4376 ⁃ 4393 . e18.

SUNG H , FERLAY J , SIEGEL R L , et al . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 ⁃ 249 .

HERBST R S , MORGENSZTERN D , BOSHOFF C . The biology and management of non⁃small cell lung cancer [J ] . Nature , 2018 , 553 ( 7689 ): 446 ⁃ 454 .

TETREAULT M P , YANG Y , KATZ J P . Kruppel⁃like factors in cancer [J ] . Nat Rev Cancer , 2013 , 13 ( 10 ): 701 ⁃ 713 .

WANG X , XIA S , LI H , et al . The deubiquitinase USP10 regulates KLF4 stability and suppresses lung tumorigenesis [J ] . Cell Death Differ , 2020 , 27 ( 6 ): 1747 ⁃ 1764 .

SHEPHERD F A , RODRIGUES PEREIRA J , CIULEANU T , et al . Erlotinib in previously treated non⁃small⁃cell lung cancer [J ] . N Engl J Med , 2005 , 353 : 123 ⁃ 132 .

ISUMI Y , HIRATA T , SAITOH H , et al . Transgenic overexpression of USP15 in the heart induces cardiac remodeling in mice [J ] . Biochem Biophys Res Commun , 2011 , 405 ( 2 ): 216 ⁃ 221 .

UHLENHOPP D J , THEN E O , SUNKARA T , et al . Epidemiology of esophageal cancer: Update in global trends, etiology and risk factors [J ] . Clin J Gastroenterol , 2020 , 13 ( 6 ): 1010 ⁃ 1021 .

SCHWEIGERT M , DUBECZ A , STEIN H J . Oesophageal cancer–An overview [J ] . Nat Rev Gastroenterol Hepatol , 2013 , 10 ( 4 ): 230 ⁃ 244 .

HANAHAN D , WEINBERG R A . Hallmarks of cancer: The next generation [J ] . Cell , 2011 , 144 ( 5 ): 646 ⁃ 674 .

GROSSBERG A J , CHU L C , DEIG C R , et al . Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma [J ] . CA Cancer J Clin , 2020 , 70 ( 5 ): 375 ⁃ 403 .

BILLER L H , SCHRAG D . Diagnosis and treatment of metastatic colorectal cancer: A review [J ] . JAMA , 2021 , 325 ( 7 ): 669 ⁃ 685 .

CATANZARO E , DEMUYNCK R , NAESSENS F , et al . Immunogenicity of ferroptosis in cancer: A matter of context? [J ] . Trends Cancer , 2024 , 10 ( 5 ): 407 ⁃ 416 .

LEE J C , MEHDIZADEH S , SMITH J , et al . Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis [J ] . Sci Immunol , 2020 , 5 ( 52 ): eaba0759 .

WU Y , YANG S , MA J , et al . Spatiotemporal immune landscape of colorectal cancer liver metastasis at single⁃cell level [J ] . Cancer Discov , 2022 , 12 ( 1 ): 134 ⁃ 153 .

SIEGEL R L , MILLER K D , FUCHS H E , et al . Cancer statistics, 2021 [J ] . CA Cancer J Clin , 2021 , 71 ( 1 ): 7 ⁃ 33 .

JIN J , XIE Y , ZHANG J S , et al . Sunitinib resistance in renal cell carcinoma: From molecular mechanisms to predictive biomarkers [J ] . Drug Resist Updat , 2023 , 67 : 100929 .

WU W , JING D , MENG Z , et al . FGD1 promotes tumor progression and regulates tumor immune response in osteosarcoma via inhibiting PTEN activity [J ] . Theranostics , 2020 , 10 ( 6 ): 2859 ⁃ 2871 .

YUAN L , LV Y , LI H , et al . Deubiquitylase OTUD3 regulates PTEN stability and suppresses tumorigenesis [J ] . Nat Cell Biol , 2015 , 17 ( 9 ): 1169 ⁃ 1181 .

PARK E J , WOO S M , MIN K J , et al . Transcriptional and post⁃translational regulation of Bim controls apoptosis in melatonin⁃treated human renal cancer Caki cells [J ] . J Pineal Res , 2014 , 56 ( 1 ): 97 ⁃ 106 .

MANNING B D , TOKER A . AKT/PKB signaling: Navigating the network [J ] . Cell , 2017 , 169 ( 3 ): 381 ⁃ 405 .

PEUGET S , ZHOU X , SELIVANOVA G . Translating p53⁃based therapies for cancer into the clinic [J ] . Nat Rev Cancer , 2024 , 24 ( 3 ): 192 ⁃ 215 .

KWON S K , SAINDANE M , BAEK K H . p53 stability is regulated by diverse deubiquitinating enzymes [J ] . Biochim Biophys Acta Rev Cancer , 2017 , 1868 ( 2 ): 404 ⁃ 411 .

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