ZMYND8 Antibody (OAAF02745)
- Known as:
- ZMYND8 Antibody (OAAF02745)
- Catalog number:
- oaaf02745
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- ZMYND8 Antibody (OAAF02745)
Related genes to: ZMYND8 Antibody (OAAF02745)
- Gene:
- ZMYND8 NIH gene
- Name:
- zinc finger MYND-type containing 8
- Previous symbol:
- PRKCBP1
- Synonyms:
- RACK7
- Chromosome:
- 20q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 1999-10-19
- Date modifiied:
- 2016-02-15
Related products to: ZMYND8 Antibody (OAAF02745)
Related articles to: ZMYND8 Antibody (OAAF02745)
- CD8 T cell exhaustion impedes control of chronic viral infection and cancer. This hypofunctional state is characterized by downregulation of the high-affinity IL-2 receptor (IL-2R) and STAT5 signalling, and differentiation from progenitor exhausted to terminally exhausted T cells rather than cytotoxic effector-like cells. The epigenetic mechanisms and regulatory networks that mediate IL-2R-STAT5 signal attenuation and loss of effector-like cell differentiation remain unknown. Here, using in vivo single-cell CRISPR screens of epigenetic factors and IL-2 signalling regulators, we reveal that the chromatin reader ZMYND8 antagonizes IL-2R-STAT5 signals to restrain effector-like states while promoting terminal exhaustion. ZMYND8 expression was upregulated by chronic antigen stimulation, and targeting ZMYND8 in CD8 T cells promoted both intermediate exhausted T cells and killer cell lectin-like receptor-expressing exhausted T cells. Accordingly, ZMYND8-deficient CD8 T cells had markedly improved antiviral and antitumour effects, especially in combination with IL-2 therapy or immune checkpoint blockade. Mechanistically, ZMYND8 bound to the active enhancer regions of the Il2ra gene locus that were co-occupied by histone acetyltransferase p300 and suppressed p300 activity. Co-deletion of p300 reversed increased IL-2R expression and effector-like cell differentiation in ZMYND8-deficient cells, suggesting that ZMYND8 represses p300-mediated transcriptional activation to curtail IL-2R-STAT5 signalling. These findings establish an epigenetic rheostat imposing 'signal 1' (chronic antigen stimulation)-induced suppression of 'signal 3' (IL-2 signalling) to enforce T cell exhaustion, with ZMYND8 deletion unleashing effector-like over terminally exhausted states and enhancing immunotherapeutic efficacy. - Source: PubMed
Publication date: 2026/09/23
Wang YanShi HaoChapman Nicole MKc AnilSun RenqiangSong HaoMeng XiaoxiSun XiangChi Hongbo - mTOR inhibitors including everolimus and temsirolimus have been approved by US FDA for treatment of clear cell renal cell carcinoma (ccRCC) in clinic. However, resistance to these drugs has been inevitable and the underlying mechanism remains poorly understood. Histone modifier ZMYND8 paradoxically acts as a transcription coactivator or corepressor. Here we show that SPOP, a CULLIN3-RING E3 ubiquitin ligase (CRL) substrate-binding protein that is often overexpressed in ccRCC in patients, promotes K63-linked polyubiquitination of ZMYND8 at lysine 398, which inhibits ZMYND8 to form phase separation compartments and drives the formation of ZMYND8-ZHX2 transactivation complex, resulting in aberrant NEK7 kinase gene transcription, alternative activation of p70S6K, and mTOR inhibitor-resistant cell growth. Inhibition of either SPOP or NEK7 increases ccRCC cell sensitivity to mTOR inhibitor. Treatment with a NEK7 proteolysis-targeting chimera (PROTAC) effectively inhibits aberrant p70S6K activation and overcame everolimus resistance in ccRCC cells in vitro and in mice. Our findings uncover a function switch of ZMYND8 driven by overexpressed SPOP as a key mechanism that causes mTOR inhibitor resistance and nominate NEK7 as a potential target of thwarting mTOR inhibitor resistance in ccRCC. - Source: PubMed
Publication date: 2026/08/25
Tang BoSun RuiShao JingweiWu Qi-YouYan YuqianWang DejieYu ZhixianHu LianxinChen YichengLiao ChenghengWei QiangBao YigeHuang Haojie - Uterine spiral artery remodelling (SAR) is a fundamental developmental process that facilitates optimal placental perfusion and supports fetal growth. Central to SAR is the phenotypic transformation of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic state, directed by invasive trophoblast cells. To advance these findings, we sought to elucidate the epigenetic mechanisms governing trophoblast-induced reprogramming of VSMC identity, enabling plasticity required for uterine vascular adaptation. - Source: PubMed
Publication date: 2026/07/15
Sarkar PoulomiAin Rupasri - The zinc finger MYND-type containing eight protein (ZMYND8) is a chromatin reader that regulates neuronal gene expression by controlling the microtubule-associated protein tau (MAPT) locus. Here, we investigate how ZMYND8 regulates expression of the long non-coding RNA MAPT213 through its interaction with GATA zinc finger domain containing 2A (GATAD2A), a component of the Nucleosome Remodelling and Deacetylase complex. ZMYND8 exhibits opposite regulatory effects on protein-coding MAPT and non-coding MAPT213 transcripts in a manner dependent on its MYND domain, promoting MAPT expression while suppressing MAPT213 levels. Chromatin immunoprecipitation experiments demonstrated that ZMYND8 specifically recruits GATAD2A to the MAPT213 internal regulatory region, establishing a direct link between protein binding and transcriptional control. We determined the crystal structure of the ZMYND8 coiled-coil MYND domain at high resolution, revealing a homodimeric architecture. The MYND domain specifically recognizes GATAD2A through direct interaction with proline-rich motifs in GATAD2A's central region. Structure-function analysis identified critical binding interface residues, while quantitative measurements revealed moderate-affinity interactions enhanced through multivalent binding mechanisms. These findings establish the molecular basis for ZMYND8-mediated recruitment of chromatin remodeling complexes to specific genomic loci and provide a structural framework for understanding transcriptional regulation of MAPT213. - Source: PubMed
Publication date: 2026/04/16
Srivastava Dushyant KumarNandi SandhikKarmakar AvradeepDas ChandrimaRoy Siddhartha - - Source: PubMed
Publication date: 2026/04/16
Cruz-Rodriguez Nataly