CDK1: beyond cell cycle regulation

Liao, Hongwei; Ji, Fang; Ying, Songmin

doi:10.18632/aging.101348

Cited by 18 publications

(15 citation statements)

References 6 publications

(5 reference statements)

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“…Cyclin B1/CDK1 kinase translocating rapidly from the cytoplasm to the nucleus is the critical target of G2 into mitosis transition (Giono et al, 2017). CDK1 promotes the DNA replicative synthesis and regulates the balance of cell cycle, thus coordinating and maintaining genomic stability, which is vital for cell survival (Liao et al, 2017). Precious studies found that CDK1-mediated regulation of cell proliferation could be modulated by regulatory subunit cyclin B1 (Jones et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Silibinin Induces G2/M Cell Cycle Arrest by Activating Drp1-Dependent Mitochondrial Fission in Cervical Cancer

You

et al. 2020

Front. Pharmacol.

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Cervical cancer is the fourth leading cancer type and the second most common gynecological malignancy among women worldwide. Silibinin (SB), a chief bioactive natural polyphenolic flavonoid of Silybum marianum L., has been used clinically for its hepatocyte protective effects. It also has anticancer effects via the induction of apoptosis and cell cycle arrest. However, the effects of SB on cervical cancer cells through mitochondrial fission have not been studied. Here, we showed that SB markedly suppressed cervical cell proliferation by inducing G2/M cell cycle arrest via the activation of dynamin-related protein 1 (Drp1), which in turn mediated the mitochondrial fission dysfunction both in vitro and in vivo. SB decreased the ATP content, mitochondrial membrane potential, and mtDNA copy number, as well as reduced the reactive oxygen species levels in cervical cells. Furthermore, SB induced excessive mitochondrial fragmentation and reduced tubule formation. Further study showed that knockdown of Drp1 abolished the SB-induced G2/M cell cycle arrest in cervical cancer cells by inhibiting the mitochondrial fission pathway. More importantly, SB inhibited Hela cell growth in vivo model. In conclusion, we are the first to demonstrate that SB induces cervical cancer cell G2/M cell cycle arrest by activating Drp1-dependent mitochondrial fission dysfunction. This study suggests the strategy of inducing Drp1-dependent mitochondrial fission for cervical cancer prevention and treatment.

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Section: Discussionmentioning

confidence: 99%

Silibinin Induces G2/M Cell Cycle Arrest by Activating Drp1-Dependent Mitochondrial Fission in Cervical Cancer

You

et al. 2020

Front. Pharmacol.

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“…However, we have recently shown, using genetic approaches, that CDK1 inhibition is enough for the synthetic lethality with MYC in mouse embryo fibroblasts as it occurs in cells deficient in CDK2, CDK4, and CDK6 [183]. It is worthy to note that CDK1 not only arrests the cell cycle but also plays a role in DNA replication and DNA repair [226]. On the other hand, MYC-induced carcinogenesis is associated to genomic instability, as demonstrated in cell culture and in mice models (reviewed in [227,228]).…”

Section: Myc-mediated Synthetic Lethality and The Cell Cyclementioning

confidence: 99%

MYC Oncogene Contributions to Release of Cell Cycle Brakes

García-Gutiérrez

Delgado

León

2019

Genes

106

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Promotion of the cell cycle is a major oncogenic mechanism of the oncogene c-MYC (MYC). MYC promotes the cell cycle by not only activating or inducing cyclins and CDKs but also through the downregulation or the impairment of the activity of a set of proteins that act as cell-cycle brakes. This review is focused on the role of MYC as a cell-cycle brake releaser i.e., how MYC stimulates the cell cycle mainly through the functional inactivation of cell cycle inhibitors. MYC antagonizes the activities and/or the expression levels of p15, ARF, p21, and p27. The mechanism involved differs for each protein. p15 (encoded by CDKN2B) and p21 (CDKN1A) are repressed by MYC at the transcriptional level. In contrast, MYC activates ARF, which contributes to the apoptosis induced by high MYC levels. At least in some cells types, MYC inhibits the transcription of the p27 gene (CDKN1B) but also enhances p27’s degradation through the upregulation of components of ubiquitin ligases complexes. The effect of MYC on cell-cycle brakes also opens the possibility of antitumoral therapies based on synthetic lethal interactions involving MYC and CDKs, for which a series of inhibitors are being developed and tested in clinical trials

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“…The top 3 ranked degree genes ( CDK1 , PLK1 , and BUB1 ) play important roles in the progression of G2/M phase in the cell cycle. 30 , 31 Furthermore, real-time PCR analysis was used to verify the results of transcriptome sequencing and the results indicated that the expression trends of the top 18 ranked degree genes were consistent with those obtained by RNA-seq, suggesting that the RNA-seq data reliably reflected the gene expression alterations ( Figure 4B ). According to the RNA-seq and real-time PCR results, the expressions of cell cycle regulated genes, such as CDK1 , PLK1 , and BUB1 , were significantly decreased after sinomenine treatment.…”

Section: Resultsmentioning

confidence: 53%

Sinomenine Inhibits the Growth of Ovarian Cancer Cells Through the Suppression of Mitosis by Down-Regulating the Expression and the Activity of CDK1

Zhu

et al. 2021

OTT

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Introduction Ovarian cancer is one of the most common gynecological cancers worldwide. While, therapies against ovarian cancer have not been completely effective, sinomenine has been proved to have anti-tumor activity in various cancer cells. However, study of its anti-ovarian cancer effect is still rare, and the underlying mechanism has not been elucidated. Therefore, we aim to explore the mechanism of sinomenine anti-ovarian cancer. Materials and Methods The effect of anti-ovarian cancer HeyA8 cells was analyzed by CCK8 and colony formation assay. The mechanism of sinomenine anti-ovarian cancer was explored via high throughput RNA-seq, and then the target mRNA and protein expression were verified by real-time PCR and Western blot, respectively. Results We found that the proliferation and clone formation ability of ovarian cancer HeyA8 cells were markedly reduced by 1.56 mM sinomenine. The transcriptome analysis showed that 2679 genes were differentially expressed after sinomenine treatment in HeyA8 cells, including 1323 down-regulated genes and 1356 up-regulated genes. Gene ontology and KEGG pathway enrichment indicated that differential expression genes (DEGs) between the groups of sinomenine and DMSO-treated HeyA8 cells were mainly involved in the process of the cell cycle, such as kinetochore organization, chromosome segregation, and DNA replication. Strikingly, the top 18 ranked degree genes in the protein–protein interaction (PPI) network were mainly involved in the process of mitosis, such as sister chromatid segregation, condensed chromosome, and microtubule cytoskeleton organization. Moreover, real-time PCR results showed consistent expression trends of DEGs with transcriptome analysis. The results of Western blot showed the expression level of CDK1, which was the highest degree gene in PPI and the main regulator controlling the process of mitosis, and the levels of phosphorylated P-CDK (Thr161) and P-Histone H3 (Ser10) were decreased after being treated with sinomenine. Conclusion Our results demonstrated that sinomenine inhibited the proliferation of HeyA8 cells through suppressing mitosis by down-regulating the expression and the activity of CDK1. The study may provide a preliminary research basis for the application of sinomenine in anti-ovarian cancer.

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CDK1: beyond cell cycle regulation

Cited by 18 publications

References 6 publications

Silibinin Induces G2/M Cell Cycle Arrest by Activating Drp1-Dependent Mitochondrial Fission in Cervical Cancer

Silibinin Induces G2/M Cell Cycle Arrest by Activating Drp1-Dependent Mitochondrial Fission in Cervical Cancer

MYC Oncogene Contributions to Release of Cell Cycle Brakes

Sinomenine Inhibits the Growth of Ovarian Cancer Cells Through the Suppression of Mitosis by Down-Regulating the Expression and the Activity of CDK1

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