Ubiquitin-like with PHD and RING finger domains protein 1 (UHRF1) (UHRF1)

Ubiquitin-like with PHD and RING finger domains protein 1 (UHRF1) is a multi-domain nuclear protein that serves as a master regulator of the epigenome, bridging DNA methylation and histone modifications. It plays a critical role in maintaining DNA methylation patterns during cell division by recognizing hemimethylated DNA through its SRA domain and recruiting DNA methyltransferase 1 (DNMT1) to the replication fork. UHRF1 also functions as an E3 ubiquitin ligase, specifically targeting histone H3 to promote chromatin remodeling and facilitate DNA replication and repair. In many human malignancies, UHRF1 is constitutively overexpressed, where it drives the silencing of tumor suppressor genes and promotes cell proliferation, migration, and survival. Due to its central role in oncogenic epigenetic reprogramming and its high expression in cancer compared to normal tissues, UHRF1 is an attractive therapeutic target. Current pharmacological strategies include small-molecule inhibitors of its reader domains and agents that induce its targeted degradation to restore the expression of silenced genes and induce apoptosis in cancer cells.

Other names

ICBP90RNF106Np95TDRD22Inverted CCAAT box-binding protein of 90 kDaRING-type E3 ubiquitin transferase UHRF1E3 ubiquitin-protein ligase UHRF1

Inhibition of E3 ubiquitin ligase activity, disruption of hemimethylated DNA binding via the SRA domain, disruption of histone H3 binding via the TTD-PHD module, and induction of proteasomal degradation or transcriptional downregulation.