Trends in Cell Biology
ReviewNew Insights into CDK Regulators: Novel Opportunities for Cancer Therapy
Section snippets
Cell Cycle and CDK Regulators: A Never-Ending Story
Cell growth and cell division require a highly regulated series of events, called the cell cycle. Over the past few decades, key components of this machinery were identified, mainly through genetic and biochemical studies in yeast. The cell cycle comprises four distinct phases: growth phase 1 (G1), DNA replication or synthesis phase (S), growth phase 2 (G2), and mitotic phase (M). Progression through these different phases is driven by cyclin-dependent kinases (CDKs) whose activities are
Ribosomal Proteins as an Emerging New Class of Cell Cycle Regulators
Ribosomal proteins (RPs) have a crucial role in cell cycle control. Ribosome synthesis and maturation is a process requiring hundreds of cofactors and occurs in the cytoplasm as well as in the nucleolus [23]. This vital process requires the coordination of three major polymerases and is tightly regulated by numerous oncogenes and tumor suppressors to accommodate the cellular demand for growth or cell cycle arrest [24,25]. 47S rRNA is synthetized in the nucleolus by RNA polymerase I and is
RPs as Targets in Cancer and Senescence-Associated Diseases
Given the important roles of CDKs in cancer progression as well as in other diseases, such as atherosclerosis, type 2 diabetes, sarcopenia, and obesity [73], extensive efforts are underway to identify novel molecules that modulate, positively or negatively, their activity. A series of small molecules that mimic CKI activities were developed to target hyperproliferative tumor cells. Flavopiridol and roscovitine were among the first generation of compounds inhibiting CDKs, but their lack in
Concluding Remarks
For more than 30 years, understanding aberrant cell cycle control in tumor cells has been a major focus of cancer research. Evasion of growth suppressors and deregulation of checkpoints are considered hallmarks of cancer. The control of the cell cycle is complex and numerous regulators have been identified, including endogenous proteins as well as synthetic compounds, such as small-molecule inhibitors. Undoubtedly, the control of cell cycle progression is not limited to the well-known
Acknowledgments
M.B. was supported by a Télévie fellowship (FNRS, Belgium). V.B. acknowledges grants from the Canadian Institutes of Health Research (CIHR, Canada) MOP-97932 and PJT-152937. G.F. acknowledges CCSRI (Canadian Cancer Society Research Institute: 704223) and the CIBC Chair for Breast Cancer Research at the CR-CHUM.
Declaration of Interests
We have no conflicts of interest to declare.
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Current address: Centre de Recherche sur le Cancer de l’Université Laval, Québec, QC, Canada