Author:
Gu Lili,Fu Yongming,Li Xiong
Abstract
AbstractUHRF1 as a member of RING-finger type E3 ubiquitin ligases family, is an epigenetic regulator with five structural domains. It has been involved in the regulation of a series of biological functions, such as DNA replication, DNA methylation, and DNA damage repair. Additionally, aberrant overexpression of UHRF1 has been observed in over ten cancer types, indicating that UHRF1 is a typical oncogene. The overexpression of UHRF1 repressed the transcription of such tumor-suppressor genes as CDKN2A, BRCA1, and CDH1 through DNMT1-mediated DNA methylation. In addition to the upstream transcription factors regulating gene transcription, post-translational modifications (PTMs) also contribute to abnormal overexpression of UHRF1 in cancerous tissues. The types of PTM include phosphorylation, acetylation, methylationand ubiquitination, which regulate protein stability, histone methyltransferase activity, intracellular localization and the interaction with binding partners. Recently, several novel PTM types of UHRF1 have been reported, but the detailed mechanisms remain unclear. This comprehensive review summarized the types of UHRF1 PTMs, as well as their biological functions. A deep understanding of these crucial mechanisms of UHRF1 is pivotal for the development of novel UHRF1-targeted anti-cancer therapeutic strategies in the future.
Funder
National Natural Science Foundation of China
National Key Clinical Specialty Construction Project
High-Level Clinical Key Speciality (Clinical Pharmacy) in Guangdong Province
Publisher
Springer Science and Business Media LLC
Reference82 articles.
1. Unoki M, Sasaki H. The UHRF protein family in epigenetics, development, and carcinogenesis. Proc Jpn Acad Ser B Phys Biol Sci. 2022;98(8):401–15.
2. Mancini M, Magnani E, Macchi F, Bonapace IM. The multi-functionality of UHRF1: epigenome maintenance and preservation of genome integrity. Nucleic Acids Res. 2021;49(11):6053–68.
3. Fujimori A, Matsuda Y, Takemoto Y, Hashimoto Y, Kubo E, Araki R, Fukumura R, Mita K, Tatsumi K, Muto M. Cloning and mapping of Np95 gene which encodes a novel nuclear protein associated with cell proliferation. Mamm Genome. 1998;9(12):1032–5.
4. Hopfner R, Mousli M, Jeltsch JM, Voulgaris A, Lutz Y, Marin C, Bellocq JP, Oudet P, Bronner C. ICBP90, a novel human CCAAT binding protein, involved in the regulation of topoisomerase IIalpha expression. Cancer Res. 2000;60(1):121–8.
5. DaRosa PA, Harrison JS, Zelter A, Davis TN, Brzovic P, Kuhlman B, Klevit RE. A Bifunctional role for the UHRF1 UBL domain in the control of hemi-methylated DNA-dependent histone ubiquitylation. Mol Cell. 2018;72(4):753-765.e6.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献