Hyperactivation of cyclin A-CDK induces centrosome overduplication and chromosome tetraploidization in mouse cells

Niwa, Tetsuo; Akaike, Yasunori; Watanabe, Kaichi; Chibazakura, Taku

doi:10.1016/j.bbrc.2021.02.079

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…Changes in the expression and regulation of CDKs induce unscheduled proliferation and chromosomal instability, well-known hallmarks of cancer and tumor aggressiveness [ 322 , 323 , 324 , 325 , 326 , 327 ]. Amplification or mutation of genes encoding CDKs, cyclins or endogenous inhibitors of CDKs have been described in many solid cancer types, and are recurrent events in the development of breast cancer [ 328 ] and GBM [ 329 ], for example.…”

Section: Protein Kinases In Pediatric Oncology and Their Association ...mentioning

confidence: 99%

Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario

et al. 2023

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Childhood cancer is considered rare, corresponding to ~3% of all malignant neoplasms in the human population. The World Health Organization (WHO) reports a universal occurrence of more than 15 cases per 100,000 inhabitants around the globe, and despite improvements in diagnosis, treatment and supportive care, one child dies of cancer every 3 min. Consequently, more efficient, selective and affordable therapeutics are still needed in order to improve outcomes and avoid long-term sequelae. Alterations in kinases’ functionality is a trademark of cancer and the concept of exploiting them as drug targets has burgeoned in academia and in the pharmaceutical industry of the 21st century. Consequently, an increasing plethora of inhibitors has emerged. In the present study, the expression patterns of a selected group of kinases (including tyrosine receptors, members of the PI3K/AKT/mTOR and MAPK pathways, coordinators of cell cycle progression, and chromosome segregation) and their correlation with clinical outcomes in pediatric solid tumors were accessed through the R2: Genomics Analysis and Visualization Platform and by a thorough search of published literature. To further illustrate the importance of kinase dysregulation in the pathophysiology of pediatric cancer, we analyzed the vulnerability of different cancer cell lines against their inhibition through the Cancer Dependency Map portal, and performed a search for kinase-targeted compounds with approval and clinical applicability through the CanSAR knowledgebase. Finally, we provide a detailed literature review of a considerable set of small molecules that mitigate kinase activity under experimental testing and clinical trials for the treatment of pediatric tumors, while discuss critical challenges that must be overcome before translation into clinical options, including the absence of compounds designed specifically for childhood tumors which often show differential mutational burdens, intrinsic and acquired resistance, lack of selectivity and adverse effects on a growing organism.

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Section: Protein Kinases In Pediatric Oncology and Their Association ...mentioning

confidence: 99%

Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario

et al. 2023

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“…CDKs belong to the serine/threonine protein kinase family, of which 20 CDK genes have been discovered so far. Although CDK monomers are inactive, after they bind with the regulatory subunit cyclin, the new complexes are active and can promote cellular events such as DNA replication and chromosome separation, as part of the cell cycle (Gopinathan et al, 2011; Niwa et al, 2021). Besides regulating the cell cycle, CDKs also have other functions in transcription, epigenetic regulation and metabolism (Guen et al, 2013; Lin et al, 2021; Sundar et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Cloning and function of the cyclin‐dependent kinase 9 gene in ovarian development of the ridgetail white prawn, Exopalaemon carinicauda

Zhang¹,

Li²,

Zheng³

et al. 2022

Aquaculture Research

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To investigate the key genes affecting ovarian development in the ridgetail white prawn, Exopalaemon carinicauda, we cloned the full‐length cDNA of the CDK9 gene and discussed its role in ovarian development. Our results show that the gene has an open reading frame of 1155 bp, encoded 383 amino acids, and it has a conserved cyclin binding motif S_TKc. The open reading frame of CDK9 was expressed as a 43.96 Kda molecular weight protein. The phylogenetic tree analysis showed that the CDK9 gene has the highest homology with the CDK9 genes of Penaeus vannamei and Penaeus japonicus. The results of qRT‐PCR show that the CDK9 gene was also expressed in the eye stalk, stomach, heart, gill, intestine, muscle, ovary, hepatopancreas and ventral cord. The expression level was highest in the ovary, which was significantly different from the other tissues (p < 0.05). In the five stages of ovarian development, the expression level of the CDK9 gene was highest in stage I, which was significantly different from the other stages (p < 0.05). In situ hybridization tests showed strong expression signals in the membrane, cytoplasm and nucleus of oocytes and previtellogenic oocytes. Nevertheless, following the proliferation of oocytes, the expression signals became much stronger in the oocyte membrane and in the whole follicular cells located in the interstitial space. The RNA interference results show that the expression of the CDK9 gene significantly affects the expression of the Vg and VgR genes. Our findings suggest that CDK9 plays an important role in the synthesis and transportation of vitellin.

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Expression of the cyclin-dependent kinase 2 gene (cdk2) influences ovarian development in the ridgetail white prawn, Exopalaemon carinicauda

Pan¹,

Hua²,

Li³

et al. 2022

Aquaculture Reports

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Hyperactivation of cyclin A-CDK induces centrosome overduplication and chromosome tetraploidization in mouse cells

Cited by 4 publications

References 38 publications

Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario

Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario

Cloning and function of the cyclin‐dependent kinase 9 gene in ovarian development of the ridgetail white prawn, Exopalaemon carinicauda

Expression of the cyclin-dependent kinase 2 gene (cdk2) influences ovarian development in the ridgetail white prawn, Exopalaemon carinicauda

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