Ask about this productRelated genes to: UHRF1 antibody
- Gene:
- UHRF1 NIH gene
- Name:
- ubiquitin like with PHD and ring finger domains 1
- Previous symbol:
- -
- Synonyms:
- ICBP90, Np95, FLJ21925, RNF106, TDRD22
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2000-03-15
- Date modifiied:
- 2017-03-17
Related products to: UHRF1 antibody
Related articles to: UHRF1 antibody
- Extracellular chromatin fragments, including cell-free DNA (cfDNA) and histones, have emerged as promising non-invasive biomarkers for cancer screening and monitoring. While aberrant DNA methylation patterns in cfDNA are already established hallmarks of cancer and are increasingly used in liquid biopsy assays, circulating histones and nucleosomes reflect complementary aspects of tumor-associated epigenetic dysregulation and chromatin remodeling. This review integrates current knowledge on intracellular and extracellular histones in cancer, highlighting their release via necrosis, apoptosis, or neutrophil extracellular traps (NETs), and their dual roles as damage-associated molecular patterns and modulators of the tumor microenvironment. We discuss the intricate mechanistic links between DNA methylation and histone modifications, histone variants, and post-translational modifications, including the bidirectional crosstalk mediated by enzymes such as DNMTs, UHRF1, and PAD4. Special emphasis is placed on NETosis and its epigenetic regulation, which further connects histone citrullination with DNA methylation machinery and tumor progression. We evaluate the clinical potential of combining cfDNA methylation profiling with circulating histone levels, histone variants, and nucleosome-associated post-translational modifications. Evidence from multiple cancer types demonstrates that multimodal epigenetic approaches, incorporating fragmentomics, histone marks, and methylation signatures, significantly improve diagnostic accuracy, tissue-of-origin identification, and early detection compared to single-modality or conventional protein biomarkers in several cancer types. Fragmentomics, reflecting nucleosome positioning and chromatin accessibility, adds a functional layer to methylation-based assays. Collectively, extracellular chromatin components offer a rich, biologically interconnected source of information. Their integrated analysis holds substantial promise for advancing precision oncology through improved screening, prognosis, treatment monitoring, and development of safer epigenetic therapies. - Source: PubMed
Publication date: 2026/09/03
Vinciguerra ManlioK Tsoneva Desislava - HIV-1 persists in cellular reservoirs of latent virus that resist antiretroviral therapy (ART) and immune clearance, necessitating novel therapeutic strategies. While "shock-and-kill" approaches aim to reactivate latent virus under immune pressure, this strategy has demonstrated limited clinical efficacy. In contrast, "block-and-lock" strategies that reinforce and maintain HIV-1 quiescence represent a complementary approach to prevent reservoir expansion and enable long-term ART-free remission. We previously demonstrated that EGCG, the major phenolic compound of green tea, reverses HIV-1 latency by inhibiting UHRF1 expression, a key regulator involved in the epigenetic silencing of HIV-1. However, EGCG exhibits poor bioavailability and dose-dependent cytotoxicity, which severely limit its clinical use. Here, we evaluated (+)-catechin:lysine 1:2, a more stable and bioavailable polyphenol complex with unexplored anti-HIV properties. In J-Lat cell subclones, high concentrations (50-300 μg/mL) of (+)-catechin:lysine 1:2 induced HIV-1 reactivation to levels comparable to those induced by EGCG, but without dose-dependent cellular toxicity. Mechanistically, HIV-1 reactivation operated through UHRF1-independent pathways, distinguishing (+)-catechin:lysine 1:2 from EGCG. Additionally, sequential vitamin C pre-treatment at a 1:2 molar ratio significantly potentiated catechin-mediated reactivation, whereas concurrent co-treatment antagonized the effect, demonstrating that precise dosing time schedules critically determined efficacy. Strikingly, short-term exposure (24 h) of therapeutically achievable low doses of (+)-catechin:lysine 1:2 (10 μg/mL) paradoxically promoted HIV-1 quiescence, suppressing spontaneous viral reactivation. Importantly, this quiescence-promoting effect was confirmed in cells isolated from ART-treated people with HIV (PWH). These findings position of (+)-catechin:lysine 1:2 as a safely administrable and bioavailable molecule with promising potential for "block-and-lock" anti-HIV-1 cure strategies. - Source: PubMed
Publication date: 2026/09/02
Bendoumou MaryamNestola LorenaDutilleul AntoinePilosio LisaNiebes PaulBurny ArsèneNecsoi CocaDe Wit StéphaneVan Lint Carine - The tandem Tudor domain (TTD) of UHRF1 is a compelling epigenetic target for novel cancer therapeutics. Here, we integrate theoretical simulations, sophisticated biophysical evaluations and cellular assays to characterize potent TTD binders. Screening of small drug- and fragment-like collections identifies several TTD ligands, with the most promising hit being the local anesthetic hydroxyprocaine. The ligand is characterized in terms of its binding requisites by calorimetry, affording a K of 1.46 μM and a well-balanced thermodynamic profile. Molecular dynamics simulations combined with heat capacity measurements and osmotic stress titrations confirm that hydroxyprocaine binds stably to the TTD by displacing approximately 26 interfacial water molecules upon complexation. A targeted follow-up screen focusing on sodium channel blockers yields two additional, although less promising hits, mexiletine and triamterene. In the DU145 prostate cancer cell line, hydroxyprocaine treatment significantly up-regulates key downstream targets including the tumor-suppressor p53 and, to a lesser degree, the stress and inflammation regulators p38 and p65, respectively, while exhibiting very low cytotoxicity. Finally, a previously undocumented interdomain interaction between TTD and its N-terminal adjacent Ubiquitin-like domain is reported, introducing a novel, potentially druggable UHRF1 regulatory feature. Together, these findings establish hydroxyprocaine as a highly viable chemical scaffold for TTD-targeted drug development. - Source: PubMed
Tsakalidis EfstratiosGiannouli MariangelaAkrani IfigeneiaPanara AnthiKatalagarianou EleniDegaita KyriakiGiahou MariaKyriakou KonstantinaRoutsi MariaNikolaou Panagiota EfstathiaTsitsou EvangeliaTsoka AggelikiVorgias Constantinos CMikros EmmanuelGikas EvangelosEfthimiadou Eleni KMyrianthopoulos Vassilios - Osteosarcoma (OS) represents a common primary malignant bone tumor associated with unfavorable clinical outcomes. Growing evidence underscores the crucial involvement of N6-methyladenosine (m6A) modifications in tumor development, but the specific mechanisms underlying the m6A regulatory network in OS remain to be elucidated. - Source: PubMed
Publication date: 2026/08/26
Song KaiLiu JuHan BowenLiu RuiZhong HuazhangTian Dasheng - Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and closely associated with persistent inflammatory responses and impairment of the mucosal barrier integrity. In this work, we demonstrated that Th17/Treg immune imbalance drove inflammation and pyroptosis in IBD, as revealed by single-cell RNA sequencing, and pyruvate kinase M2 (PKM2) and ubiquitin-like with PHD and RING finger domains 1 (Uhrf1) displayed a negative correlation in IBD clinic samples. Target fishing analysis revealed that eupatolide (EPT) covalently bound to C165 of PKM2 with a dissociation constant (K) of 106 nM, corroborated by follow-up chemical biology assays. We gained a deeper understanding of the mechanistic by which EPT interfered PKM2 function, specifically by promoting its interaction with Uhrf1, enhancing the K48-linked ubiquitylation and degradation of PKM2 to block its nuclear translocation. Critically, PKM2 silencing mitigated dextran sodium sulfate (DSS)-driven inflammation and pyroptosis across in vitro and in vivo models, with EPT showing no further efficacy upon PKM2 knockdown in IBD mice. This work uncovered Uhrf1-dependent PKM2 ubiquitination/degradation as a previously unrecognized therapeutic axis for IBD, while positioning EPT as a molecular glue capable of targeting the Uhrf1-PKM2 complex. - Source: PubMed
Publication date: 2026/08/25
Zhang JuanXu Xin-RongZhang Hui-LinZhu Qi-MengLi Xin-YuanShang Xi-PengDu Jing-HuiMorisseau ChristopheQiu FengSun Cheng-Peng