Zhx2 Antibody - C-terminal region (ARP37944_P050)
- Known as:
- Zhx2 Antibody - C-terminal region (ARP37944_P050)
- Catalog number:
- arp37944_p050
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- Zhx2 Antibody - C-terminal region (ARP37944_P050)
Related genes to: Zhx2 Antibody - C-terminal region (ARP37944_P050)
- Gene:
- ZHX2 NIH gene
- Name:
- zinc fingers and homeoboxes 2
- Previous symbol:
- -
- Synonyms:
- KIAA0854
- Chromosome:
- 8q24.13
- Locus Type:
- gene with protein product
- Date approved:
- 2004-01-22
- Date modifiied:
- 2015-08-24
Related products to: Zhx2 Antibody - C-terminal region (ARP37944_P050)
Related articles to: Zhx2 Antibody - C-terminal region (ARP37944_P050)
- The von Hippel-Lindau (VHL) gene encodes the core substrate-recognition subunit of the Cullin2-RING E3 ubiquitin ligase complex, regulating cellular oxygen sensing and proteostasis. While targeting the canonical VHL-hypoxia-inducible factor (HIF) axis (e.g. belzutifan) has improved advanced clear cell renal cell carcinoma (ccRCC) management, intrinsic non-responsiveness and acquired resistance to HIF-2α inhibitors present major clinical limitations. Expanding beyond the HIF-centric paradigm reveals a broader network of non-canonical VHL targets, offering new opportunities for therapeutic development across ccRCC and pan-cancer contexts. This review provides an evidence-graded synthesis of novel VHL targets spanning epigenetic regulation (e.g. ZHX2, SETDB1, METTL3/METTL14), metabolic reprogramming (e.g. NDRG3, TFAM), extracellular matrix architecture (e.g. fibronectin, COL4A2), and immune modulation (e.g. TBK1). Supporting evidence across these targets ranges from direct biochemical ubiquitination to indirect downstream observations, derived predominantly from preclinical cell-line and xenograft models. Disruption of VHL and these non-HIF networks contributes to oncogenesis across diverse malignancies. Translating these mechanistic insights catalyzes two distinct therapeutic modalities. For VHL-deficient malignancies, selectively intercepting unshielded downstream effectors with small-molecule inhibitors provides rational, vulnerability-targeted salvage strategies. Conversely, in VHL-proficient malignancies, the exceptional chemical tractability of VHL has been repurposed by proteolysis targeting chimeras (PROTACs). VHL-recruiting PROTACs hijack operational ligase machinery to degrade targeted oncogenic drivers, including some previously "undruggable" oncogenes. These next-generation degraders offer potential biomarker-driven strategies to overcome current therapeutic bottlenecks in ccRCC and other associated malignancies. However, current evidence derives predominantly from in vitro and animal models. Realizing the clinical potential of VHL-targeted strategies requires addressing key unresolved questions regarding substrate directness, tissue tropism, and resistance trade-offs. Further investigating these core mechanistic and pharmacological bottlenecks will be essential to guide next-generation therapies in VHL-associated malignancies. - Source: PubMed
Publication date: 2026/09/09
Deng RuiyiWang BoyuanZou MingruiMao KaiyuanShang JiahengQiu JianhuiZhou JingchengXu HuaMa XinWang YizhouCai LinGong Kan - Transcription factors (TFs) are key players in eukaryotic gene regulation, but the DNA binding specificity of many TFs remains unknown. Here, we assay 284 mostly uncharacterized putative human TFs using selective microfluidics-based ligand enrichment followed by sequencing (SMiLE-seq), revealing 74 new DNA binding motifs. To investigate whether TFs lacking detectable motifs preferably bind epigenetically modified DNA, we develop methylation-sensitive SMiLE-seq (meSMiLE-seq), a microfluidic assay that simultaneously probes binding to methylated and unmethylated DNA. Using meSMiLE-seq, we assay 114 TFs and identify DNA-binding models for 48 proteins, including known methylation-sensitive binding modes for POU5F1 and RFX5. 11 TFs prefer methylated DNA or display alternative methylation-dependent motifs (e.g. PRDM13), while 13 show aversion to methylated sequences (e.g. USF3). Finally, we identify ZHX2 as a putative Z-DNA binder. Altogether, our study significantly expands the human TF codebook, while providing a versatile platform to quantitatively assay the impact of DNA modifications on TF binding. - Source: PubMed
Publication date: 2026/08/05
Gralak Antoni JFaltejskova KaterinaYang Ally W HSteiner ClemenceRusseil JulieGrenningloh NadiaInukai SachiDemir MustafaDainese RiccardoOwen CooperPankevich Eugenia V Hughes Timothy RKulakovskiy Ivan VKribelbauer-Swietek Judith Fvan Mierlo GuidoDeplancke Bart - Based on findings from human atherosclerotic arteries and mouse arterial injury models, where ZHX2 expression is significantly downregulated, this study identifies ZHX2 as a critical inhibitor of pathological vascular remodeling. Functionally, local adenoviral overexpression of ZHX2 in vivo attenuates neointima formation in a mouse carotid artery ligation model, while in vitro experiments demonstrate that ZHX2 impedes the proliferation and migration of primary Vascular Smooth Muscle Cells (VSMCs). Mechanistically, integrated RNA-seq and ChIP-seq analyses reveal that ZHX2 transcriptionally regulates GADD45G, directly binding to its promoter and activating its transcription. The essential role of this pathway is confirmed by the finding that knockdown of GADD45G counteracts the inhibitory effects of ZHX2 overexpression on VSMC proliferation, migration, and neointima formation. Consequently, the ZHX2/GADD45G signaling axis is highlighted as a potential regulatory pathway in injury-associated neointimal remodeling. - Source: PubMed
Fan SiyuanWu XuelianGui LinWu YichenQiao BaoruLi YueZheng ZheHuang Kai - Neuroblastoma (NB) is the most common malignant extracranial solid tumor in children, with poor prognosis, inadequate therapeutic responses, and high recurrence rates. Zinc fingers and homeoboxes protein 2 (ZHX2) functions in various cancers, but its role in NB remains unclear. Retinoic acid (RA) has been used as a pro-differentiation agent in NB, but its limited response rate necessitates novel combinations. This study aims to explore key transcription factors (TFs) in improving RA efficacy and NB prognosis. - Source: PubMed
Publication date: 2026/05/02
Wang YanLiu WeiweiLi DongMa HuixianLiu LinghongZhang AijunJu Xiuli - Colorectal cancer (CRC) is the most prevalent digestive system malignancy worldwide. The development of targeted therapeutics specifically effective for CRC is currently in dire need. Preclinical studies showed that CDK4/6 inhibitor palbociclib suppressed the growth of CRC, but whether this effect is durable is unclear. In this study, we aimed to evaluate the roles of palbociclib-induced senescence and find a new strategy to maximize its effectiveness in CRC treatment. Animal and cellular experiments revealed that palbociclib-induced senescence and the senescence-associated secretory phenotype (SASP) caused drug resistance, anti-apoptosis, PD-L1 upregulation and inhibition of CD8 T cells' function. Using CRISPR/Cas9 screening, we identified MCL1 as a senolytic target to eliminate palbociclib-induced senescent CRC cells in the presence of palbociclib. Mechanically, palbociclib-induced senescent cells upregulated ZHX2 and its transcriptional target MCL1, rendered their resistance to apoptosis and T cell-mediated cytotoxicity, whereases combining palbociclib with MCL1 inhibitor markedly induced apoptosis in senescent cells by activating both extrinsic and intrinsic apoptotic pathways. Lastly, we proposed a seno-therapy consisting of a palbociclib pre-treatment plus a combination treatment of palbociclib and MCL1 inhibitor and found it effectively inhibited tumor growth and improved the survival of CRC xenografted mice. Besides its senolytic effect, seno-therapy also reduced PD-L1-positive cells and enhancing the cytotoxic functions of CD8 T cells. In conclusion, co-targeting CDK4/6 and MCL1 efficiently eliminates palbociclib-induced senescent CRC cells and offers a promising CDK4/6 inhibitor-based strategy for CRC treatment, ensuring prolonged tumor suppression and reducing the risk of progression or recurrence. - Source: PubMed
Publication date: 2026/03/24
Wang HaiyangShen TianqiYang SuisuiZhou XiaohuiCao PingpingYu HongHe KexinFu MinYu HanyangLiu XiaorongZhou TingtingWang JingHuang MingdeQian XuWang XiuxingWang QianghuLiu LiFan ZhiningZhang YingjianLin Fan