UFMylation: A promising post‑translational modification in cancer therapy

BAI Rui; SUN Wenjie

doi:10.14188/j.1671-8852.2025.0075

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UFMylation: A promising post‑translational modification in cancer therapy

更新时间：2026-11-05

- UFMylation: A promising post‑translational modification in cancer therapy
- Medical Journal of Wuhan University Vol. 46, Issue 5, Pages: 677-682(2025)
- 作者机构：
  
  1.武汉大学中南医院肺部肿瘤科湖北武汉 430071
  2.郑州大学附属肿瘤医院/河南省肿瘤医院放射肿瘤科河南郑州 450000
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2025.0075
  CLC： R730
- Received：23 January 2025，
  
  Published：25 May 2025
- 稿件说明：
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白睿,孙文洁.UFMylation:癌症治疗中一种有前景的翻译后修饰[J].武汉大学学报（医学版）,2025,46(05):677-682.

BAI Rui,SUN Wenjie.UFMylation: A promising post‑translational modification in cancer therapy[J].Medical Journal of Wuhan University,2025,46(05):677-682.
白睿,孙文洁.UFMylation:癌症治疗中一种有前景的翻译后修饰[J].武汉大学学报（医学版）,2025,46(05):677-682. DOI： 10.14188/j.1671-8852.2025.0075.

BAI Rui,SUN Wenjie.UFMylation: A promising post‑translational modification in cancer therapy[J].Medical Journal of Wuhan University,2025,46(05):677-682. DOI： 10.14188/j.1671-8852.2025.0075.

摘要

UFMylation是一种新发现的翻译后修饰，发生在各种生物体中。UFM1与泛素类似，通过三步酶促反应共价连接到其底物上。与泛素化不同的是，泛素化涉及多种E1、E2和E3酶，UFMylation只涉及每种酶中的一种。许多研究表明，UFMylation涉及各种细胞过程。UFM1级联的异常与各种疾病，尤其是肿瘤密切相关。本文对UFMylation的过程和功能进行综述，重点介绍了UFMylation在各种癌症发生和发展中的作用及其分子机制，旨在为肿瘤的治疗提供新的靶点和策略。

Abstract

UFMylation is a newly discovered post‑translational modification that occurs in various organisms. UFM1 is similar to ubiquitin and covalently attaches to its substrate through a three‑step enzymatic reaction. Unlike ubiquitination

which involves multiple E1

and E3 enzymes

UFMylation involves only one of each type of enzyme. Many studies have shown that UFMylation involves various cellular processes. Abnormalities in the UFM1 cascade are closely related to various diseases

especially tumors. This article reviews the process and function of UFMylation

with a focus on its role and molecular mechanisms in the occurrence and development of various cancers

to identify new targets and strategies for the treatment of tumors.

关键词

Keywords

references

HERHAUS L , DIKIC I . Expanding the ubiquitin code through post‑translational modification [J ] . EMBO Rep , 2015 , 16 ( 9 ): 1071 ‑ 1083 .

LEE J M , HAMMARÉN H M , SAVITSKI M M , et al . Control of protein stability by post‑translational modifications [J ] . Nat Commun , 2023 , 14 : 201 .

KOMATSU M , INADA T , NODA N N . The UFM1 system: Working principles, cellular functions, and pathophysiology [J ] . Mol Cell , 2024 , 84 ( 1 ): 156 ‑ 169 .

FAN Z H , XU L , GAO Y , et al . The cytoplasmic‑nuclear transport of DDX3X promotes immune‑mediated liver injury in mice regulated by endoplasmic reticulum stress [J ] . Cell Death Dis , 2024 , 15 : 702 .

ZHAO C , LUO J , ZHANG Y , et al . Temperature‑dependent lifespan extension is achieved in miR‑80‑deleted Caenorhabditis elegans by NLP‑45 to modulate endoplasmic reticulum unfolded protein responses [J ] . Aging Cell , 2025 , 24 ( 1 ): e14345 .

WANG X , GENG J , RIMAL S , et al . The p53 target DRAM1 modulates calcium homeostasis and ER stress by promoting contact between lysosomes and the ER through STIM1 [J ] . Proc Natl Acad Sci USA , 2024 , 121 ( 39 ): e2400531121 .

RAKHE N , BHATT L K . Valosin‑containing protein: A potential therapeutic target for cardiovascular diseases [J ] . Ageing Res Rev , 2024 , 101 : 102511 .

ZHAO W B , SHENG R . The correlation between mitochondria‑associated endoplasmic reticulum membranes (MAMs) and Ca 2+ transport in the pathogenesis of diseases [J ] . Acta Pharmacol Sin , 2025 , 46 : 271 ‑ 291 .

CHAU D D , YU Z C , CHAN W W R , et al . The cellular adaptor GULP1 interacts with ATG14 to potentiate autophagy and APP processing [J ] . Cell Mol Life Sci , 2024 , 81 ( 1 ): 323 .

PANICHNANTAKUL P , AGUILAR L C , DAYNARD E , et al . Protein UFMylation regulates early events during ribosomal DNA‑damage response [J ] . Cell Rep , 2024 , 43 ( 9 ): 114738 .

WANG Z , XIONG S , WU Z , et al . VCP/p97 UFMylation stabilizes BECN1 and facilitates the initiation of autophagy [J ] . Autophagy , 2024 , 20 ( 9 ): 2041 ‑ 2054 .

LEE L , PEREZ OLIVA A B , MARTINEZ‑BALSALOBRE E , et al . UFMylation of MRE11 is essential for telomere length maintenance and hematopoietic stem cell survival [J ] . Sci Adv , 2021 , 7 ( 39 ): eabc7371 .

CHE G L , XIAO X , LI T Y , et al . Ufmylation: A potential modification for neurological diseases [J ] . Curr Neuropharmacol , 2025 . DOI: 10.2174/011570159X340639240905092813 http://dx.doi.org/10.2174/011570159X340639240905092813 .

YAN T X , HECKMAN M G , CRAVER E C , et al . The UFMylation pathway is impaired in Alzheimer's disease [J ] . Mol Neurodegener , 2024 , 19 ( 1 ): 97 .

WANG L , XU Y , FUKUSHIGE T , et al . Mono‑UFMylation promotes misfolding‑associated secretion of α‑synuclein [J ] . Science Advances , 2024 , 10 ( 11 ): eadk2542 .

ZHOU J , MA X , HE X , et al . Dysregulation of PD‑L1 by UFMylation imparts tumor immune evasion and identified as a potential therapeutic target [J ] . Proc Natl Acad Sci USA , 2023 , 120 ( 11 ): e2215732120 .

TAO Y J , YIN S L , LIU Y , et al . UFL1 promotes antiviral immune response by maintaining STING stability independent of UFMylation [J ] . Cell Death Differ , 2023 , 30 : 16 ‑ 26 .

WANG S X , LIU Y Y , SU M , et al . UFMylation is involved in serum inflammatory cytokines generation and splenic T cell activation induced by lipopolysaccharide [J ] . Cytokine , 2024 , 183 : 156755 .

ZHOU X C , MAHDIZADEH S J , LE GALLO M , et al . UFMylation: A ubiquitin‑like modification [J ] . Trends Biochem Sci , 2024 , 49 ( 1 ): 52 ‑ 67 .

KANG S H , KIM G R , SEONG M , et al . Two novel ubiquitin‑fold modifier 1 (UFM1)‑specific proteases, UFSP1 and UFSP2 [J ] . J Biol Chem , 2007 , 282 ( 8 ): 5256 ‑ 5262 .

KOMATSU M , CHIBA T , TATSUMI K , et al . A novel protein‑conjugating system for UFM1, a ubiquitin‑fold modifier [J ] . EMBO J , 2004 , 23 ( 9 ): 1977 ‑ 1986 .

TATSUMI K , SOU Y S , TADA N , et al . A novel type of E3 ligase for the UFM1 conjugation system [J ] . J Biol Chem , 2010 , 285 ( 8 ): 5417 ‑ 5427 .

XIE R , WANG M , ZHOU W , et al . Long non‑coding RNA (LncRNA) UFC1/miR‑34a contributes to proliferation and migration in breast cancer [J ] . Med Sci Monit , 2019 , 25 : 7149 ‑ 7157 .

YOO H M , KANG S H , KIM J Y , et al . Modification of ASC1 by UFM1 is crucial for ERα transactivation and breast cancer development [J ] . Mol Cell , 2014 , 56 ( 2 ): 261 ‑ 274 .

YOO H M , PARK J H , KIM J Y , et al . Modification of ERα by UFM1 increases its stability and transactivity for breast cancer development [J ] . Mol Cells , 2022 , 45 ( 6 ): 425 ‑ 434 .

FANG B , LI Z , QIU Y , et al . Inhibition of UBA5 expression and induction of autophagy in breast cancer cells by usenamine A [J ] . Biomolecules , 2021 , 11 ( 9 ): 1348 .

YANG J J , ZHOU Y L , XIE S D , et al . Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer [J ] . J Exp Clin Cancer Res , 2021 , 40 ( 1 ): 206 .

MAO M , CHEN Y , YANG J , et al . Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD‑L1 levels in triple‑negative breast cancer [J ] . J Immunother Cancer , 2022 , 10 ( 12 ): e005668 .

KIM C H , NAM H S , LEE E H , et al . Overexpression of a novel regulator of p120 catenin, NLBP, promotes lung adenocarcinoma proliferation [J ] . Cell Cycle , 2013 , 12 ( 15 ): 2443 ‑ 2453 .

DA SILVA S R , PAIVA S L , BANCERZ M , et al . A selective inhibitor of the UFM1‑activating enzyme, UBA5 [J ] . Bioorg Med Chem Lett , 2016 , 26 ( 18 ): 4542 ‑ 4547 .

TERAI H , KITAJIMA S , POTTER D S , et al . ER stress signaling promotes the survival of cancer "persister cells" tolerant to EGFR tyrosine kinase inhibitors [J ] . Cancer Res , 2018 , 78 ( 4 ): 1044 ‑ 1057 .

LIN J X , XIE X S , WENG X F , et al . UFM1 suppresses invasive activities of gastric cancer cells by attenuating the expres7sion of PDK1 through PI3K/AKT signaling [J ] . J Exp Clin Cancer Res , 2019 , 38 ( 1 ): 410 .

LIN J X , XIE X S , WENG X F , et al . Low expression of CDK5RAP3 and DDRGK1 indicates a poor prognosis in patients with gastric cancer [J ] . World J Gastroenterol , 2018 , 24 ( 34 ): 3898 ‑ 3907 .

ZHENG C H , WANG J B , LIN M Q , et al . CDK5RAP3 suppresses Wnt/β‑catenin signaling by inhibiting AKT phosphorylation in gastric cancer [J ] . J Exp Clin Cancer Res , 2018 , 37 ( 1 ): 59 .

WANG J B , WANG Z W , LI Y , et al . CDK5RAP3 acts as a tumor suppressor in gastric cancer through inhibition of β‑catenin signaling [J ] . Cancer Lett , 2017 , 385 : 188 ‑ 197 .

HU Z H , WANG X H , LI D , et al . UFBP1, a key component in ufmylation, enhances drug sensitivity by promoting proteasomal degradation of oxidative stress‑response transcription factor Nrf2 [J ] . Oncogene , 2021 , 40 : 647 ‑ 662 .

ZHOU J , MA X , XU L , et al . Genomic profiling of the UFMylation family genes identifies UFSP2 as a potential tumour suppressor in colon cancer [J ] . Clin Transl Med , 2021 , 11 ( 12 ): e642 .

LIU J , GUAN D , DONG M G , et al . UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination [J ] . Nat Cell Biol , 2020 , 22 : 1056 ‑ 1063 .

YU T , SHAN T D , LI J Y , et al . Knockdown of linc‑UFC1 suppresses proliferation and induces apoptosis of colorectal cancer [J ] . Cell Death Dis , 2016 , 7 : e2228 .

KWON J , CHO H J , HAN S H , et al . A novel LZAP‑binding protein, NLBP, inhibits cell invasion [J ] . J Biol Chem , 2010 , 285 ( 16 ): 1 2232‑ 12240 .

CHEN E , ZHOU B , BIAN S , et al . The lncRNA B3GALT5‑AS1 functions as an HCC suppressor by regulating the miR‑934/UFM1 axis [J ] . J Oncol , 2021 , 2021 : 1776432 .

MAK G W , CHAN M M , LEONG V Y , et al . Overexpression of a novel activator of PAK4, the CDK5 kinase‑associated protein CDK5RAP3, promotes hepatocellular carcinoma metastasis [J ] . Cancer Res , 2011 , 71 ( 8 ): 2949 ‑ 2958 .

MAK G W , LAI W L , ZHOU Y , et al . CDK5RAP3 is a novel repressor of p14ARF in hepatocellular carcinoma cells [J ] . PLoS One , 2012 , 7 ( 7 ): e42210 .

ZHAO J J , PAN K , LI J J , et al . Identification of LZAP as a new candidate tumor suppressor in hepatocellular carcinoma [J ] . PLoS One , 2011 , 6 ( 10 ): e26608 .

WANG K , CHEN S Y , WU Y , et al . The ufmylation modification of ribosomal protein L10 in the development of pancreatic adenocarcinoma [J ] . Cell Death Dis , 2023 , 14 : 350 .

LI G , LIAO C , CHEN J , et al . Targeting the MCP‑GPX4/HMGB1 axis for effectively triggering immunogenic ferroptosis in pancreatic ductal adenocarcinoma [J ] . Adv Sci (Weinh) , 2024 , 11 ( 21 ): e2308208 .

ZHUO R , ZHANG Z M , CHEN Y L , et al . CDK5RAP3 is a novel super‑enhancer‑driven gene activated by master TFs and regulates ER‑Phagy in neuroblastoma [J ] . Cancer Lett , 2024 , 591 : 216882 .

XI P , DING D , ZHOU J , et al . DDRGK1 regulates NF‑κB activity by modulating IκBα stability [J ] . PLoS One , 2013 , 8 ( 5 ): e64231 .

HE C , XING X X , CHEN H Y , et al . UFL1 ablation in T cells suppresses PD‑1 UFMylation to enhance anti‑tumor immunity [J ] . Mol Cell , 2024 , 84 ( 6 ): 1120 ‑ 1138.e8 .

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