ArticleCell proliferation2022
High abundance of CDC45 inhibits cell proliferation through elevation of HSPA6.
Article in Cell proliferation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 31 citations in OpenAlex.
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- CDC45 promotes the stemness and metastasis in lung adenocarcinoma by affecting the cell cycle.Journal of translational medicine · 2024Article
- Deciphering the molecular functionality of Cdc45 in replisomal complex.Biochemistry and biophysics reports · 2024Article
- Visfatin Affects the Transcriptome of Porcine Luteal Cells during Early Pregnancy.International journal of molecular sciences · 2024Article
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- Transcriptomic analysis of stem cells from chorionic villi uncovers the impact of chromosomes 2, 6 and 22 in the clinical manifestations of Down syndrome.Stem cell research & therapy · 2023Article
- DYRK1-mediated phosphorylation of endocytic components is required for extracellular lumen expansion in ascidian notochord.Biological research · 2023Article
- High abundance of CDC45 inhibits cell proliferation through elevation of HSPA6.Cell proliferation · 2022Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
objectivesCDC45 is the core component of CMG (CDC45-MCMs-GINS) complex that plays important role in the initial step of DNA replication in eukaryotic cells. The expression level of cdc45 is under the critical control for the accurate cell cycle progression. Loss-of-function of cdc45 has been demonstrated to inhibit cell proliferation and leads to cell death due to the inhibition of DNA replication and G1-phase arrest. An increasing of CDC45 inhibits cell proliferation as well. Nevertheless, a systematic analysis of the effect of high dose of CDC45 on cell physiology and behaviors is unclear. In the present study, we aimed to investigate the effects and mechanisms of high dose of CDC45 on cell behaviors. MATERIALS AND
methodsWe overexpressed cdc45 in cultured cell lines, Ciona and Drosophila embryos, respectively. The cell cycle progression was examined by the BrdU incorporation experiment, flow cytometry and PH3 (phospho-Histone 3) staining. RNA-sequencing analysis and qRT-PCR were carried out to screen the affected genes in HeLa cells overexpressing cdc45. siRNA-mediated knockdown was performed to investigate gene functions in HeLa cells overexpressing cdc45.
resultsWe found that high level of cdc45 from different species (human, mammal, ascidian, and Drosophila) inhibited cell cycle in vitro and in vivo. High dose of CDC45 blocks cells entering into S phase. However, we failed to detect DNA damage and cell apoptosis. We identified hspa6 was the most upregulated gene in HeLa cells overexpressing cdc45 via RNA-seq analysis and qRT-PCR validation. Overexpression of Hs-hspa6 inhibited proliferation rate and DNA replication in HeLa cells, mimicking the phenotype of cdc45 overexpression. RNAi against hspa6 partially rescued the cell proliferation defect caused by high dose of CDC45.
conclusionsOur study suggests that high abundance of CDC45 stops cell cycle. Instead of inducing apoptosis, excessive CDC45 prevents cell entering S phase probably due to promoting hspa6 expression.
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