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
- FLT3-ITD mutations in acute myeloid leukemias (AMLs) cause ligand-independent signaling. One way signaling pathways potently and immediately influence cell fates is by phosphorylating key fate-determining proteins to trigger their proteolysis. We investigated the master transcription factor (MTF) driver of granulo-monocytic lineage-fates, CEBPA, for regulation by this mechanism because we found high CEBPA mRNA but little CEBPA protein in versus -wildtype AML cells, and inhibiting FLT3-ITD signaling with tyrosine kinase inhibitors (TKI) rapidly rescued CEBPA protein. Mass spectrometry revealed that CEBPA interacts with major ubiquitin-proteasome pathway (UPP) components: the ubiquitin-ligase UHRF1 and the deubiquitinase USP7. TKI treatment decreased the phosphorylation of CEBPA (Ser21) and USP7 (Ser18) alongside shifts in CEBPA interactions from degradative UHRF1 to protective USP7, stabilizing CEBPA and activating differentiation. Similarly, TKIs and UPP inhibitors stabilized the USP7 client p53, triggering apoptosis specifically in FLT3-ITD cells. Notably, UPP inhibitors (such as bortezomib) successfully stabilized CEBPA and p53 even in TKI-resistant cells. Because FLT3-ITD signaling functionally suppresses CEBPA and p53, genetic mutations in or were mutually exclusive with FLT3-ITD in clinical series. In summary, FLT3-ITD drives the UPP-mediated destruction of CEBPA and p53, positioning UPP inhibitors as promising therapeutic candidates acting downstream of TKIs. - Source: PubMed
Publication date: 2026/07/30
Saunthararajah YogenGu XiaorongBiswas SudiptaZahran ZeinabBae SongaBalusu RameshJha BabalMaciejewski Jaroslaw - Targeted protein degradation represents a promising therapeutic strategy, yet its broader application is often limited by the scarcity of usable E3 ligases. Glutathione peroxidase 4 (GPX4) is a key target for inducing ferroptosis, but achieving sustained and potent inhibition remains challenging with conventional enzymatic inhibitors. Herein, we report the first small-molecule GPX4 degraders that incorporate either electrophilic warheads or a minimal azide group as an E3 recruitment ligand. The azide-based degrader DK-5070 effectively drives potent GPX4 degradation, achieving a DC of 17.4 nM and a Dmax of 84%, thereby outperforming larger PROTAC-based degraders. Notably, DK‑5070 exhibits potent antitumor activity both in vitro (IC = 47.21 nM) and in vivo (TGI = 41.8%), demonstrating significant efficacy as a GPX4 degrader. Mechanistic studies reveal that degradation is mediated through recruitment of the oncogenic E3 ligase UHRF1, which is frequently overexpressed in tumors, underscoring the potential for tumor-specific protein degradation. This demonstrated small-molecule degraders that recruit UHRF1 to facilitate targeted degradation of GPX4. In this system, the azide group functions as a minimal recruitment ligand, thereby expanding the E3 ligase toolbox and offering a promising strategy for targeted cancer therapy. - Source: PubMed
Publication date: 2026/08/19
Lin ZehongDuan KangWan RuiJiang TaoWei JinzheSun MiaoSkryl'nikova Mariia AGureev Maxim AZhang Zhi-MinZhang ZhangDing KeMa NanLiu TongzhengTan YiLi Zhengqiu - Cytoplasmic lattices (CPLs) are filamentous assemblies essential for mammalian embryonic development. They are known to regulate organelle organization, spindle assembly, and protein homeostasis, but their molecular functions remain unclear. Here, we develop a strategy combining cryo-focused ion beam milling and cryo-electron tomography to resolve macromolecular complexes directly in mammalian embryos. Using this approach, we determine the in situ structure of cytoplasmic lattices within 6/8-cell mouse embryos at ~4.7 Å resolution. CPL filaments are built from multiple copies of at least fourteen proteins arranged into a ~4.5 MDa repeating unit. The repeat contains a central cavity that is open at the back and lined with multiple FBXW-SKP1 complexes and three modules, each containing the E2 ubiquitin-conjugating enzyme UBE2D and the E3 ligase UHRF1. We resolve two CPL states: one is consistent with a ubiquitin-charged UBE2D, where ubiquitin is held in an open, inactive conformation by binding the scaffold protein PADI6; the second lacks discernible ubiquitin density and shows structural changes compatible with ubiquitin becoming available for transfer. Our findings support a model in which CPLs function as large ubiquitin ligase assemblies during early embryonic development. - Source: PubMed
Publication date: 2026/08/10
Singh KashishHarasimov KatarinaNiakan Kathy KCarter Andrew P - Osteophytes are a characteristic feature of osteoarthritis (OA), and clarifying their molecular regulation may contribute to preventive and therapeutic strategies. Uhrf1 (ubiquitin-like containing PHD and RING finger domains 1), a regulator of DNA methylation maintenance, is indispensable for chondrocyte proliferation and differentiation in the growth plate. Because osteophytes develop via endochondral ossification, we hypothesized that Uhrf1 is involved in osteophyte formation. platelet-derived growth factor receptor α (PDGFRα)-lineage cell-specific Uhrf1-knockout mice showed that Uhrf1 regulates the proliferation and chondrogenic potential of synovial PDGFR-α-lineage cells during osteophyte development, influencing osteophyte formation. Furthermore, experiments using human synovial cells revealed that UHRF1 maintains DNA methylation and identified NLK (nemo-like kinase) as a candidate gene that may be regulated by UHRF1-mediated DNA methylation. These findings suggest that UHRF1 may modulate Wnt signaling and chondrogenic differentiation through the regulation of NLK. Together, these results highlight the role of Uhrf1 in osteophyte formation and provide insight into the mechanisms underlying OA progression, suggesting Uhrf1-mediated pathways as targets for OA. - Source: PubMed
Publication date: 2026/07/31
Jono AkihiroYanagihara YutaSakai HiroshiSaeki NoritakaKutsuna TatsuhikoKinoshita TomofumiUezumi AkiyoshiTakao MasakiImai Yuuki - After fertilization, maternally deposited mRNAs are cleared, and de novo transcription is initiated through zygotic genome activation (ZGA), a core event of the maternal-to-zygotic transition in mice. 2-cell-like cells (2CLCs), a rare MERVL-positive subpopulation of mouse embryonic stem cells, partially recapitulate transcriptional features of 2-cell embryos. Although canonical MERVL-high 2CLCs depend on DUX, Dux knockout embryos can develop to term, suggesting that 2CLC models do not fully capture DUX-independent pathways associated with preimplantation transcriptional programs. Here, we show that disruption of C-terminal binding protein 1/2 (Ctbp1/2) activates both DUX-dependent minor ZGA-associated genes and DUX-independent major ZGA- and post-ZGA-associated programs. Pramel7 is derepressed independently of DUX and contributes to subsets of both programs. PRAMEL7 overexpression partially rescues transcriptional defects caused by Dux deletion and is associated with UHRF1 downregulation and DNA demethylation-linked activation of post-ZGA-associated genes. These findings identify CtBP1/2 as repressors of multiple early embryonic transcriptional programs in mouse embryonic stem cells. - Source: PubMed
Publication date: 2026/08/03
Yoshioka KazumaIchisakino MakiSugiyama KotaHayakawa NaoAbadi Selma AlamandaYoon HeekyoungMarutani MiyuMasuda RyoTakahashi KyoSeki Yoshiyuki