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

Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is a multi-domain epigenetic regulator that plays a critical role in maintaining DNA methylation patterns during cell division (Source: UniProt Q96T88). It functions as a molecular bridge by recruiting DNA methyltransferase 1 (DNMT1) to hemi-methylated DNA sites through its SRA (Set and Ring Associated) domain, while simultaneously recognizing specific histone modifications via its Tandem Tudor Domain (TTD) and Plant Homeodomain (PHD) (Source: NCBI Gene 29128). Additionally, UHRF1 acts as an E3 ubiquitin ligase, ubiquitinating histone H3 to further facilitate the recruitment and activation of DNMT1 at the replication fork. In many human malignancies, UHRF1 is significantly overexpressed, which correlates with the silencing of tumor suppressor genes and poor clinical prognosis (Source: PubMed 28655771). Because of its central role in oncogenic epigenetic reprogramming, UHRF1 is a high-priority therapeutic target. Current drug discovery efforts focus on small molecules that can disrupt its protein-protein interactions or inhibit its enzymatic domains to restore normal gene expression profiles in cancer cells (Source: PubMed 30654574).

Other names

Np95ICBP90RNF106E3 ubiquitin-protein ligase UHRF1Nuclear zinc finger protein Np95Inverted CCAAT box-binding protein of 90 kDa

Inhibition of UHRF1 binding to hemi-methylated DNA, disruption of the UHRF1-DNMT1 complex, inhibition of E3 ubiquitin ligase activity, and antagonism of the Tandem Tudor Domain (TTD) or Plant Homeodomain (PHD) to prevent histone recognition (Source: PubMed ID 30654574, 33500415).