Cyclin‐dependent protein kinases: Key regulators of the eukaryotic cell cycle

Abstract

Passage through the cell cycle requires the successive activation of different cyclin-dependent protein kinases (CDKs). These enzymes are controlled by transient associations with cyclin regulatory subunits, binding of inhibitory polypeptides and reversible phosphorylation reactions. To promote progression towards DNA replication, CDK/cyclin complexes phosphorylate proteins required for the activation of genes involved in DNA synthesis, as well as components of the DNA replication machinery. Subsequently, a different set of CDK/cyclin complexes triggers the phosphorylation of numerous proteins to promote the profound structural reorganizations that accompany the entry of cells into mitosis. At present, much research is focused on elucidating the links between CDK/cyclin complexes and signal transduction pathways controlling cell growth, differentiation and death. In future, a better understanding of the cell cycle machinery and its deregulation during oncogenesis may provide novel opportunities for the diagnostic and therapeutic management of cancer and other proliferation-related diseases.

Cell cycle regulated expression and phosphorylation of hpttg proto-oncogene product

“…A burst of phosphorylation events drives the cell through M phase of the cell cycle (King et al, 1994). Numerous proteins become phosphorylated, resulting in important changes in their structure or activity (Nigg, 1991). The appearance and increase of mitosis-promoting factor (MPF) kinase activity characterize M phase.…”

“…The appearance and increase of mitosis-promoting factor (MPF) kinase activity characterize M phase. MPF consists of a Cdc2 and cyclin B complex (reviewed by Nigg, 1995). Late in M phase the ubiquitinization of the cyclin B subunit triggers cytokinesis and allows progression to G1 (reviewed in King et al, 1994).…”

“…Late in M phase the ubiquitinization of the cyclin B subunit triggers cytokinesis and allows progression to G1 (reviewed in King et al, 1994). Cdc2 phosphorylates a wide range of targets and can act both as a regulator of mitosis, triggering cascades of reactions by activating downstream protein kinases, or directly phosphorylating some of the proteins that are supposed to bring about certain metabolic and structural changes (Nigg, 1991). In this context, identi®cation of the critical Cdc2 substrates is necessary to understand how mitosis is regulated and executed.…”

K-ras modulates the cell cycle via both positive and negative regulatory pathways

“…The cell cycle of mammalian cells is regulated by a very complex machinery, of which cyclins and cyclin dependent protein kinases (CDKs) play essential roles (reviewed in Pines, 1995;Nigg, 1995). Multiple cyclin-CDK complexes undergo changes in the kinase and cyclin moieties which are believed to drive the cell cycle from one stage to another.…”

G 2 /M cell cycle arrest on HT-29 cancer cells and toxicity assessment of triphenylphosphanegold(I) carbonimidothioates, Ph 3 PAu[SC(OR) = NPh], R = Me, Et, and iPr, during zebrafish development

“…An early event in apoptosis is loss of plasma membrane asymmetry which results in the exposure of phosphatidylserine (PS) residues at the outer plasma membrane leaflet [27]. As annexin V interacts strongly and specifically with PS, the measurement of annexin V can be employed to monitor apoptosis.…”