Ask about this productRelated genes to: WDHD1 antibody
- Gene:
- WDHD1 NIH gene
- Name:
- WD repeat and HMG-box DNA binding protein 1
- Previous symbol:
- -
- Synonyms:
- AND-1, CTF4, CHTF4
- Chromosome:
- 14q22.2-q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-11-13
- Date modifiied:
- 2018-02-13
Related products to: WDHD1 antibody
Related articles to: WDHD1 antibody
- has been identified as a crucial oncogene in various tumors, but its role in pancreatic cancer remains unexplored. This study investigated the mechanisms by which WDHD1 contributes to pancreatic cancer progression. Differential analysis of the Cancer Genome Atlas (TCGA) pancreatic cancer samples identified abnormally expressed genes. Cellular assays, including cell proliferation, flow cytometry, and apoptosis assays, demonstrated WDHD1's oncogenic role. WDHD1 expression was significantly elevated in pancreatic cancer cells and tissues compared to normal counterparts. Knockdown of WDHD1 inhibited cell proliferation, induced apoptosis, and caused G1-phase cell-cycle arrest. xenograft models further validated that WDHD1 knockdown suppressed the growth of pancreatic cancer cells. Mechanistically, WDHD1 knockdown resulted in significant reductions in CDK4 and cyclin D1 protein levels, whereas WDHD1 overexpression produced the opposite effects. Additionally, E2F1 overexpression increased the expression of at both mRNA and protein levels. Rescue experiments revealed that WDHD1 knockdown could reverse the E2F1-induced upregulation of CDK4 and cyclin D1 protein levels. In conclusion, E2F1 promotes pancreatic cancer cell proliferation and cell-cycle progression by upregulating WDHD1, which in turn enhances the expression of the CDK4-cyclin D1 complex. - Source: PubMed
Publication date: 2026/03/26
Yang XiaojuanZhang ZhiweiLv ShuangjuanZhang BuzheTao XueLiu ChangZhu Qing - DNA replication is carried out by the replisome and is essential for maintaining genome integrity and cell proliferation. Pathogenic variants in genes encoding various replisome components cause microcephalic primordial dwarfism (MPD), characterized by growth retardation, microcephaly, and developmental abnormalities. Here, we report bi-allelic hypomorphic variants in WDHD1 as a cause of MPD with a broad spectrum of additional abnormalities, including acute liver failure, in 17 subjects from 14 families. WDHD1 encodes a replisome scaffolding protein (also known as AND-1 and Ctf4), which is essential for replisome assembly, replication fork stability, and sister chromatid cohesion. We found aberrant splicing of WDHD1 pre-mRNAs for all intronic variants tested and markedly reduced WDHD1 protein levels in subject-derived fibroblasts. Fibroblasts with bi-allelic WDHD1 variants showed globally reduced replication fork speed and impaired replication control, accompanied by spontaneous DNA damage and a G1-to-S transition defect. Using various cell biology approaches, we show that subject fibroblasts displayed reduced proliferation, abnormal nuclear morphology, including micronuclei, multilobed, and enlarged nuclei, as well as an increased number of metaphases with premature sister chromatid separation. Together, our findings establish WDHD1 as a protein required for normal organismal growth and development in humans and underscore its multiple functions in maintaining genome integrity. - Source: PubMed
Publication date: 2026/04/09
Tibbe DeboraVogt Marie RonjaHolling TessSchlieben Lea DewiKortüm FannyShoukier MoneefBagowski ChristophDistelmaier FelixAverdunk LuisaKnaus AlexejKrawitz PeterKuechler AlmaLainka ElkeStalke Amelievon Hardenberg SandraAuber BerndPfister Eva-DoreenReversade BrunoSabbagh AnthonyBertoli-Avella Aida MAlawbathani SalemPalmer Elizabeth EChauhan ManishaRius RocioKim Yoonji Papingi DzhoyBartholdi DeborahBraun DominiqueMaier OliverDinwiddie AprilSteichen-Gersdorf ElisabethJanecke Andreas RTiulpakov AnatolyZernov NikolayArismendi Maria IzabelJorge Alexander A LGoel HimanshuDreyer LaurenLoughman LilyProkisch HolgerBorgmann KerstinKutsche Kerstin - HCC is a highly vascularized solid tumor that develops rapidly and has a poor prognosis. Previous studies have shown that fibroblasts and angiogenesis in the tumor microenvironment play significant roles in the progression of HCC, and the combined effect of both on HCC is worth exploring. Therefore, we developed the CAF-VEGF prognostic scoring model to assess the prognosis of HCC patients. Single-cell sequencing was done on cancer tissues and nearby normal tissues in the study using data that we downloaded from the GEO database. We used the CellChat and Monocle3 packages to analyze the angiogenesis pathways and differentiation trajectories of fibroblasts. Subsequently, we conducted functional enrichment on fibroblasts. We constructed the CAF-VEGF prognostic model using the COX and LASSO algorithms and evaluated its prognostic value through survival and ROC curves. Based on the prognostic model, we identified key genes through differential expression screening, WGCNA, and PPI network analysis. The conclusions were ultimately validated by expression experiments and functional assays. We found that fibroblasts had a higher infiltration rate in HCC tissues and successfully constructed a CAF-VEGF prognostic model in HCC, proving its effectiveness. Using the CAF-VEGF score, we identified the key molecular markers ESCO2 and WDHD1, both significantly upregulated in HCC cells. Their overexpression may lead to poor prognosis in HCC patients. Additionally, through experiments, we found that both can promote angiogenesis and enhance the proliferation and invasion-migration abilities of HCC cells. This study successfully constructed the CAF-VEGF prognostic model for HCC, and may help improve the prognosis of HCC patients. We also found that the genes WDHD1 and ESCO2 can promote HCC infiltration by regulating angiogenesis, providing insights for future HCC treatment. - Source: PubMed
Zheng HaoTang ShengweiShi RuidaZhu YantingGeng XitongHuang ShuhanZhang RuiyuQu XiaoyuWan HaoFang ChenshuoWang XinZhu YeFeng YuhongHuang DaJiang Weifan - WD repeat and HMG-box DNA binding protein 1 (WDHD1) is dysregulated in various tumors; however, its role in hepatocellular carcinoma (HCC) remains unexplored. Herein, we observed that WDHD1 was significantly upregulated in HCC tissues and cell lines and correlated with poor prognosis. Regulatory analysis identified hsa-miR-22, hsa-miR-139, and the transcription factors EP300 and CREBBP as potential modulators of WDHD1. Functional assays revealed that WDHD1 knockdown suppressed cell proliferation, migration, and invasion, whereas its overexpression enhanced these oncogenic phenotypes both in vitro and in vivo. Furthermore, WDHD1 depletion promoted cellular apoptosis. Mechanistically, WDHD1 interacted with components of the CDC45-MCM-GINS (CMG) complex and maintained their structural integrity, thereby facilitating cell cycle progression. Drug sensitivity analysis indicated that elevated WDHD1 expression enhanced responsiveness to cell cycle-targeting agents. Additionally, high WDHD1 levels were associated with increased CD4 memory T cell infiltration, elevated tumor mutational burden (TMB), and enhanced expression of key immune checkpoint markers, suggesting a potential for improved response to immunotherapy in these patients. These findings suggest WDHD1 as a novel oncogenic driver and promising therapeutic target in HCC. - Source: PubMed
Publication date: 2026/03/17
Xiang ZhengHuang XianfengZhu ShimaoZhang XianGuo JiejieChen YujieHuang ZhimingHu Shanshan - Short linear motifs (SLiMs) in disordered protein regions direct numerous protein-protein interactions, yet most remain uncharacterized. The Asn-Pro-Phe (NPF) motif is a well-known EH-domain ligand implicated in endocytosis, but here we reveal that the non-catalytic subunit of human DNA polymerase ε (POLE2) also serves as a general NPF-motif receptor. Using a quantitative "native holdup" assay, we find that POLE2 selectively binds diverse NPF-containing peptides, including canonical EH-domain ligands (e.g., SYNJ1) and previously uncharacterized motifs. Biochemical measurements and mutational analyses show that NPF motifs interact with a shallow pocket near the POLE2 C-terminus, and AlphaFold predictions confirm key roles for Y513, E520, and S522 in motif coordination. Proteome-scale affinity screens identify NPF-containing nuclear proteins (e.g., WDHD1, DONSON, TTF2) that bind POLE2 with micromolar affinities, and their motif mutations abolish binding in cell extracts. Although POLE2 primarily tethers the catalytic POLE subunit to replication forks, these results indicate that it can also recruit various NPF-bearing partners involved in replication, DNA repair, and transcription regulation. Notably, NPF motifs optimized for EH-domain binding can still associate with POLE2, highlighting the inherent degeneracy of SLiM-mediated networks. Overall, these findings establish POLE2 as a central hub possibly linking replication with other processes via broad NPF-motif recognition. - Source: PubMed
Publication date: 2025/12/13
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