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Post-translational modification is a rite of passage for cellular functional proteins and ultimately regulate almost all aspects of life. Ubiquitin-fold modifier 1 (UFM1) system represents a newly identified ubiquitin-like modification system with indispensable biological functions, and the underlying biological mechanisms remain largely undiscovered. The field has recently experienced a rapid growth of research revealing that UFMylation directly or indirectly regulates multiple immune processes. Here, we summarised important advances that how UFMylation system responds to intrinsic and extrinsic stresses under certain physiological or pathological conditions and safeguards immune homeostasis, providing novel perspectives into the regulatory framework and functions of UFMylation system, and its therapeutic applications in human diseases.
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http://dx.doi.org/10.1002/ctm2.70019 | DOI Listing |
BMB Rep
August 2025
Department of Biochemistry, College of Life Science and Technology, Institute for Bio-medical Convergence Science and Technology, Yonsei University, Seoul 03722, Korea.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex metabolic disorder that encompasses a spectrum of conditions, from simple hepatic steatosis to metabolicassociated steatohepatitis (MASH). MASH is characterized by inflammation and accelerated fibrosis progression, which can ultimately lead to cirrhosis and hepatocellular carcinoma. Given its steadily increasing prevalence, MASLD has emerged as a global health epidemic.
View Article and Find Full Text PDFSci Adv
July 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China/College of Pharmacy, Jinan University, Guangzhou 510632, China.
() can function as a tumor suppressor or oncogene depending on context, but its role in colorectal cancer (CRC) is not well understood. Here, we demonstrate that BAP1 suppresses CRC progression primarily by deubiquitinating and stabilizing von Hippel-Lindau tumor suppressor protein (pVHL). BAP1 undergoes covalent modification by ubiquitin-fold modifier 1 (UFM1) at Lys, Lys, Lys, and Lys, enhancing its interaction with pVHL and promoting pVHL stabilization.
View Article and Find Full Text PDFbioRxiv
May 2025
London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, United Kingdom.
Host cells contest invasion by intracellular bacterial pathogens with multiple strategies that recognise and / or damage the bacterial surface. To identify novel host defence factors targeted to intracellular bacteria, we developed a versatile proximity biotinylation approach coupled to quantitative mass spectrometry that maps the host-bacterial interface during infection. Using this method, we discovered that intracellular and become targeted by UFM1-protein ligase 1 (UFL1), an E3 ligase that catalyses the covalent attachment of Ubiquitin-fold modifier 1 (UFM1) to target substrates in a process called UFMylation.
View Article and Find Full Text PDFJ Virol
July 2025
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA.
Post-translational modifications play crucial roles in regulating viral infections, yet roles for many modifications remain unexplored in orthoflavivirus biology. Here, we demonstrate that the UFMylation system, a post-translational modification pathway that catalyzes the transfer of UFM1 onto proteins and promotes infection by multiple orthoflaviviruses, including dengue virus (DENV), Zika virus (ZIKV), West Nile virus, and yellow fever virus. We found that depletion of the UFMylation E3 ligase complex proteins UFL1 and UFBP1, as well as other UFMylation machinery components (UBA5, UFC1, and UFM1), significantly reduces orthoflavivirus infectious virion production.
View Article and Find Full Text PDFMol Med Rep
July 2025
Department of General Surgery, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Protein post‑translational modifications (PTMs) play crucial roles in various life activities and aberrant protein modifications are closely associated with numerous major human diseases. Ubiquitination, the first identified protein modification system, involves the covalent attachment of ubiquitin molecules to lysine residues of target proteins. UFMylation, a recently discovered ubiquitin‑like modification, shares similarities with ubiquitination.
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