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Review
. 2025 Jul 22;68(1):68.
doi: 10.1007/s12016-025-09079-6.

UHRF1 in Immune Regulation and Diseases: Mechanisms and Therapeutic Implications

Tingyue Guo  1   2 , Yihui Ruan  3 , Bo Wu  1 , Shulan Sun  4 , Hongxu Liu  5   6
Affiliations
Review

UHRF1 in Immune Regulation and Diseases: Mechanisms and Therapeutic Implications

Tingyue Guo et al. Clin Rev Allergy Immunol. .

Abstract

As a key epigenetic regulator, E3 ubiquitin-ligase ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is essential for maintaining genomic stability. The aberrant activation of UHRF1 has been strongly implicated in cancer progression. Emerging evidence indicates that UHRF1 serves as a pivotal orchestrator of immune homeostasis. This review provides an overview of the impact of UHRF1 on both innate and adaptive immunity, highlighting its epigenetic and regulatory roles in the development and function of macrophages, T lymphocytes, and B lymphocytes. Crucially, the protective mechanisms of UHRF1 in autoimmune disorders while concurrently detailing its tumor-promoting functions are dissected. Finally, this review discusses the therapeutic challenges and future perspectives for targeting UHRF1 in autoimmune disorders and cancers.

Keywords: Adaptive immune system; Cytokines; Innate immune system; UHRF1.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

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References

    1. Wang L, Yang X, Zhao K, Huang S, Qin Y, Chen Z et al (2024) MOF-mediated acetylation of UHRF1 enhances UHRF1 E3 ligase activity to facilitate DNA methylation maintenance. Cell Rep 43(3):113908 - PubMed
    1. Liu Y, Hrit JA, Chomiak AA, Stransky S, Hoffman JR, Tiedemann RL et al (2024) DNA hypomethylation promotes UHRF1-and SUV39H1/H2-dependent crosstalk between H3K18ub and H3K9me3 to reinforce heterochromatin states. Mol Cell 85(2):394–412
    1. Madakashira BP, Magnani E, Ranjan S, Sadler KC (2024) DNA hypomethylation activates Cdk4/6 and Atr to induce DNA replication and cell cycle arrest to constrain liver outgrowth in zebrafish. Nucleic Acids Res 52(6):3069–3087 - PubMed - PMC
    1. Tian D, Tang J, Geng X, Li Q, Wang F, Zhao H et al (2020) Targeting UHRF1-dependent DNA repair selectively sensitizes KRAS mutant lung cancer to chemotherapy. Cancer Lett 493:80–90 - PubMed - PMC
    1. Zhao J, Chen X, Song G, Zhang J, Liu H, Liu X (2017) Uhrf1 controls the self-renewal versus differentiation of hematopoietic stem cells by epigenetically regulating the cell-division modes. Proc Natl Acad Sci U S A 114(2):E142–E151 - PubMed

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