In this paper we propose a role for the CDC 6 protein in the entry of cells into mitosis. This has not been considered in the literature so far. Recent experiments suggest that CDC 6 , upon entry into mitosis, inhibits the appearance of active CDK 1 and cyclin B complexes. This paper proposes a mathematical model which incorporates the dynamics of kinase CDK 1 , its regulatory protein cyclin B, the regulatory phosphatase CDC 25 and the inhibitor CDC 6 known to be involved in the regulation of active CDK 1 and cyclin B complexes. The experimental data lead us to formulate a new hypothesis that CDC 6 slows down the activation of inactive complexes of CDK 1 and cyclin B upon mitotic entry. Our mathematical model, based on mass action kinetics, provides a possible explanation for the experimental data. We claim that the dynamics of active complexes CDK 1 and cyclin B have a similar nature to diauxic dynamics introduced by Monod in 1949. In mathematical terms we state it as the existence of more than one inflection point of the curve defining the dynamics of the complexes.
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http://dx.doi.org/10.3390/cells8121537 | DOI Listing |
Clin Drug Investig
January 2025
Department of Public Health Sciences, University of Virginia, 560 Ray C Hunt Dr., Room 2107, Charlottesville, VA, USA.
Background And Objective: Cyclin-dependent kinase (CDK)4/6 inhibitors in combination with endocrine therapy (ET) significantly enhance progression-free survival and overall survival in patients diagnosed with HR+/HER2- metastatic breast cancer (MBC). However, they are highly expensive, and their economic impact has not been fully evaluated. This is a retrospective secondary analysis evaluating the cost effectiveness of these drugs, differentiating between medication-related and non-medication costs from a healthcare perspective.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Departamento de Biologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14040-901, SP, Brazil.
In the flower development study, we identified SCI1 (Stigma/style Cell-cycle Inhibitor 1), a regulator of cell proliferation. SCI1 interacts with NtCDKG;2 ( Cyclin-Dependent Kinase G;2), a homolog of human CDK11, which is responsible for RanGTP-dependent microtubule stabilization, regulating spindle assembly rate. In a Y2H screening of a cDNA library using NtCDKG;2 as bait, a RanBP1 (Ran-Binding Protein 1) was revealed as its interaction partner.
View Article and Find Full Text PDFInt J Oncol
February 2025
Department of Pathology, GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Center, 6229HX Maastricht, The Netherlands.
Human papillomavirus (HPV)‑positive and -negative head and neck squamous cell carcinoma (HNSCC) are often associated with activation of the phosphatidylinositol 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway due to mutations or amplifications in , loss of or activation of receptor tyrosine kinases. In HPV‑negative tumors, (encoding p16 protein) inactivation or (encoding Cyclin D1 protein) amplification frequently results in sustained cyclin‑dependent kinase (CDK) 4/6 activation. The present study aimed to investigate the efficacy of the CDK4/6 inhibitors (CDKi) palbociclib and ribociclib, and the PI3K/Akt/mTOR pathway inhibitors (PI3Ki) gedatolisib, buparlisib and alpelisib, in suppressing cell viability of HPV‑positive and ‑negative HNSCC cell lines.
View Article and Find Full Text PDFDev Growth Differ
January 2025
Amphibian Research Center, Hiroshima University, Higashi-Hiroshima, Japan.
Cyclin-dependent kinases (CDKs) are key regulators of cell cycle progression, in conjunction with cyclins. The cyclin-CDK system is highly conserved among eukaryotes, and CDK1 is considered essential for progression through the M phase. However, the extent to which cell cycle progression depends on CDK1 varies between cell types.
View Article and Find Full Text PDFNPJ Breast Cancer
January 2025
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA.
Optimal timing and dosing of adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitor in early breast cancer is controversial. This prospective phase II clinical trial investigated tolerability and safety of two ribociclib dosing schedules. Patients with stage I-III hormone receptor-positive (HR+)/HER2- breast cancer on adjuvant endocrine therapy (ET) were randomized to two ribociclib dosing schedules: 400 mg continuous vs 600 mg intermittent, with initiation in early (prior ET < 2 years) vs delayed (prior ET ≥ 2 years) setting.
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