Ask about this productRelated genes to: CDC45L antibody
- Gene:
- CDC45 NIH gene
- Name:
- cell division cycle 45
- Previous symbol:
- CDC45L2, CDC45L
- Synonyms:
- -
- Chromosome:
- 22q11.21
- Locus Type:
- gene with protein product
- Date approved:
- 1998-09-08
- Date modifiied:
- 2014-11-19
Related products to: CDC45L antibody
Related articles to: CDC45L antibody
- We integrated bulk, single-cell, and spatial transcriptomics to test whether intratumoral heterogeneity (ITH) aggravates CD8 T-cell exhaustion (TEX) in lung adenocarcinoma. In bulk cohorts, ITH and TEX were tightly coupled, with ITH-High tumors preferentially exhibiting deeper TEX phenotypes. This dually adverse (high ITH/high TEX) context was associated with increased antigenicity (higher TMB, predicted neoantigen and cancer/testis antigen scores) but reduced TCR diversity, lower global immune/stromal infiltration, more aggressive clinicogenomic features, and poorer survival. Joint ITH-TEX stratification further revealed an additive prognostic effect, with dual-low (low ITH/low TEX) best and dual-high (high ITH/high TEX) worst outcomes. Single-cell analyses implicated macrophages: ITH-High tumors exhibited coordinated upregulation of classical MHC-I antigen-presentation programs (processing/loading; HLA-A/B/C signaling), stronger macrophage→TEX communication, and enrichment of terminal TEX states. Spatially, in ITH-High tumors, TEX co-localized more closely with MHC-I macrophage niches than with macrophages overall, whereas in ITH-Low tumors this proximity was attenuated. B cells showed increased TEX communication but inconsistent MHC-I state spatial coupling, while dendritic cells showed high proximity without ITH-dependent communication increases and weakened colocalization when restricted to MHC-I. We also derived a six-gene decision-tree classifier (CDC45, CENPF, PCLAF, SCGB3A1, CDCA8, and NDC80) predicting ITH/TEX phenotypes. These data support a macrophage MHC-I axis linking ITH to terminal TEX and motivate combining checkpoint blockade with macrophage reprogramming or modulation of antigen-processing and presentation. - Source: PubMed
Publication date: 2026/04/25
Yin ShangzhenGao HaiyanLi QiangWang MengruiZhang PengGuo YurouNan PengyuKong WeihaoShen HongmeiWang LiqiangLu Jianping - Chemoresistance to cisplatin is a major contributor to the progression of head and neck squamous cell carcinoma (HNSCC); however, the mechanisms underlying cisplatin resistance in HNSCC remain incompletely understood. Dysregulation of metabolite transport between mitochondria and the cytoplasm, mediated by solute carrier family 25 (SLC25), is closely associated with tumor progression. Solute carrier family 25 member 1 (SLC25A1) promotes malignant phenotypes in various cancers; however, its role in HNSCC remains unexplored. Here, we demonstrate that SLC25A1 is overexpressed in HNSCC and is closely associated with poor prognosis. SLC25A1 upregulation promotes cisplatin resistance in HNSCC cells. Moreover, SLC25A1 enhances cisplatin resistance in HNSCC cells by inducing cellular senescence. Mechanistically, SLC25A1 upregulates the expression of RANBP1, CDC45, and PES1 through histone H3 lysine 27 acetylation-mediated transcriptional activation. Furthermore, SLC25A1 interacts with HSPD1, a mitochondrial chaperonin protein, via its C-terminal region to increase citrate transport and cytosolic acetyl-CoA levels. Treatment with CTPI-2, a specific inhibitor of SLC25A1, exhibits therapeutic effects against cisplatin-resistant HNSCC. These findings establish SLC25A1 as a key regulator of cisplatin resistance in HNSCC, suggesting that it serves as both a predictive biomarker and a potential therapeutic target in chemoresistant HNSCC. From a translational perspective, these results support CTPI-2 as a promising therapeutic agent for overcoming cisplatin resistance. - Source: PubMed
Publication date: 2026/04/10
Li JingYang TaoLi YunYang XinjieHe YaodongYao YanbingZhao ShengnanLiu RongYang ZihuiZhang HongxinWang QianLi HuanWei Jianhua - DNA replication initiation requires local melting of fully base-paired DNA for a helicase to gain a foothold and initiate processive DNA unwinding. In eukaryotes and archaea, the helicase engine is the hexameric ring minichromosome maintenance (MCM) complex. In eukaryotes, a defined biochemical sequence assembles two Cdc45-MCM-GINS (CMG) complexes that provide limited DNA unwinding as the species that immediately precedes extensive unwinding. A prior structure revealed how MCM subunits interact with this form of DNA, but the atomic progression from undistorted DNA to this melted DNA species is unknown. Here, we present a sequential DNA melting mechanism determined by snapshots of an archaeal MCM ring with DNA in varying degrees of melting. In this mechanism, successive ATP-binding at MCM ATPase sites drives sequential discrete DNA melting steps mediated a specific MCM aromatic residue. Analysis of eukaryotic structures shows loaded MCM rings principally adopt only two molecular arrangements at the ATPase: one that does not melt DNA and one tuned to melt DNA with equivalent aromatic residues, indicating a universal sequential mechanism melts DNA in archaea and eukaryotes for replication initiation. - Source: PubMed
Publication date: 2026/03/31
Rasouli SanazMyasnikov AlexanderEnemark Eric J - Cyclin-dependent kinase 1 (CDK1) is a key regulator of cell cycle progression and a potential therapeutic target for invasive malignancies. However, developing selective CDK1 inhibitors with manageable toxicity remains a significant challenge. In this study, a novel series of 1,2,4-triazolobenzene sulfonamide derivatives were designed and synthesized based on the structure of JNJ7706621 and its derivative 3n, and subjected to comprehensive bioactivity evaluation and structure-activity relationship discussion. Among them, 11l emerged as a highly promising lead compound, exhibiting nanomolar inhibitory activity against CDK1 (IC = 5.5 nM) with high selectivity over CDK2, Aurora A, and CDK4, showing selectivity indices of 4.7-, 14.1-, and 73.2-fold, respectively. In vitro, 11l exhibited broad antiproliferative activity, particularly against HCT116 colon cancer cells. Unlike conventional kinase inhibitors that solely suppress catalytic activity, 11l induced G2/M phase arrest and downregulated CDK1, cyclin B1, and the replication initiation factor CDC45. Further investigation revealed that 11l induces severe DNA replication stress, subsequently activating the p53 signaling pathway to trigger apoptosis. This mechanism was recapitulated in CDC45 knockdown models. In vivo efficacy evaluation demonstrated that 30 mg/kg 11l achieved a tumor growth inhibition (TGI) rate of 56.4%, without inducing significant body weight loss or observable organ toxicity. Collectively, these findings identify 11l as a safe CDK1 inhibitor with a distinct mechanism of action, supporting its potential as a promising therapeutic strategy for cancer treatment. - Source: PubMed
Publication date: 2026/03/25
Wu LingjieWang NingLu YiWang YangMa LieenLou GaojieWang NanJiang AiliDing LijianHe ShanZhang Bin - Here we describe a damaging heterozygous variant in CDC45 in an individual with common variable immunodeficiency (CVID) and recurrent viral infections. This individual has variably decreased number of circulating NK cells, disruption in the ratio of CD56 to CD56 cells, and consistently decreased NK cell function. Interestingly, the inherited CDC45 variant is also present in a sibling with less severe clinical manifestations; we determined that allelic bias of the damaging allele accounts for this differential expressivity. As previously reported for other helicase variants that cause inborn errors of immunity (IEI), we found cell cycle defects in immune cells from the proband that lead to reduced survival of NK cells. Together, these findings link another member of the core replicative helicase complex to inborn errors of immunity and highlight the sensitivity of NK cells to these variants. They also define another case of allelic bias contributing to variable expressivity of an IEI gene. - Source: PubMed
Publication date: 2026/03/06
Guilz Nicole CAhn Yong-OonSeo SeungmaeSaturne Madrikha DConte Matilde IShehzad Sana RHegewisch-Solloa EverardoPedroza Luis AlbertoCastillo MicahGunaratne PreethiChinn Ivan KLupski James RMace Emily M