Ubiquitin fold modifier 1 (UFM1) is a newly identified post-translational modifier that is involved in the UFMylation process. Similar to ubiquitination, UFMylation enables the conjugation of UFM1 to specific target proteins, thus altering their stability, activity, or localization. UFM1 chains have the potential to undergo cleavage from their associated proteins via UFM1-specific proteases, thus highlighting a reversible feature of UFMylation. This modification is conserved across nearly all eukaryotic organisms, and is associated with diverse biological activities such as hematopoiesis and the endoplasmic reticulum stress response. The disruption of UFMylation results in embryonic lethality in mice and is associated with various human diseases, thus underscoring its essential role in embryonic development, tissue morphogenesis, and organismal homeostasis. In this review, we aim to provide an in-depth overview of the UFMylation system, its importance in disease processes, and its potential as a novel target for therapeutic intervention.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41401-024-01456-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Multifaceted roles of UFMylation in health and disease.
Acta Pharmacol Sin
January 2025
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, 250014, China.
Ubiquitin fold modifier 1 (UFM1) is a newly identified post-translational modifier that is involved in the UFMylation process. Similar to ubiquitination, UFMylation enables the conjugation of UFM1 to specific target proteins, thus altering their stability, activity, or localization. UFM1 chains have the potential to undergo cleavage from their associated proteins via UFM1-specific proteases, thus highlighting a reversible feature of UFMylation.
View Article and Find Full Text PDFUfmylation: a potential modification for neurological diseases.
Curr Neuropharmacol
January 2025
Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Neurological disorders are the leading health threats worldwide, characterized by impairments in consciousness, cognition, movement, and sensation, and can even lead to death. UFMylation is a novel post-translational modification (PTM) that serves as an important regulatory factor, promoting the complexity of protein structures and enhancing the diversity and specificity of functions. In UFMylation, ubiquitin-fold modifier 1 (UFM1) is covalently transferred to the primary amine of a lysine residue on the target protein through the synergistic action of three enzymes: the activating enzyme E1 of UFM1, the coupling enzyme E2 of UFM1, and the ligase E3.
View Article and Find Full Text PDFMithramycin targets head and neck cancer stem cells by inhibiting Sp1 and UFMylation.
Cancer Cell Int
December 2024
Laboratory for Personalized Medicine, Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, Zagreb, 10000, Croatia.
Background: The development of resistance to therapy is characteristic of head and neck squamous cell carcinoma (HNSCC), the 6th most common cancer, and is often attributed to cancer stem cells (CSCs). By proteomic approach, we determined that UFMylation plays an important role in HNSCC CSCs. Because of the necessity for innovative therapeutic strategies, we explore here the therapy targeting CSCs based on mithramycin and its inhibitory effect on Sp1 transcription factor, UFMylation, and CSCs survival and stemness.
View Article and Find Full Text PDFThe UFMylation pathway is impaired in Alzheimer's disease.
Mol Neurodegener
December 2024
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, 32224, USA.
Background: Alzheimer's disease (AD) is characterized by the presence of neurofibrillary tangles made of hyperphosphorylated tau and senile plaques composed of beta-amyloid. These pathognomonic deposits have been implicated in the pathogenesis, although the molecular mechanisms and consequences remain undetermined. UFM1 is an important, but understudied ubiquitin-like protein that is covalently attached to substrates.
View Article and Find Full Text PDFFunctional profiling of murine glioma models highlights targetable immune evasion phenotypes.
Acta Neuropathol
November 2024
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
Cancer-intrinsic immune evasion mechanisms and pleiotropy are a barrier to cancer immunotherapy. This is apparent in certain highly fatal cancers, including high-grade gliomas and glioblastomas (GBM). In this study, we evaluated two murine syngeneic glioma models (GL261 and CT2A) as preclinical models for human GBM using functional genetic screens, single-cell transcriptomics and machine learning approaches.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!