Phosphorylation network dynamics in the control of cell cycle transitions

Abstract

SummaryFifteen years ago, it was proposed that the cell cycle in fission yeast can be driven by quantitative changes in the activity of a single protein kinase complex comprising a cyclin -namely cyclin B -and cyclin dependent kinase 1 (Cdk1). When its activity is low, Cdk1 triggers the onset of S phase; when its activity level exceeds a specific threshold, it promotes entry into mitosis. This model has redefined our understanding of the essential functional inputs that organize cell cycle progression, and its main principles now appear to be applicable to all eukaryotic cells. But how does a change in the activity of one kinase generate ordered progression through the cell cycle in order to separate DNA replication from mitosis? To answer this question, we must consider the biochemical processes that underlie the phosphorylation of Cdk1 substrates. In this Commentary, we discuss recent findings that have shed light on how the threshold levels of Cdk1 activity that are required for progression through each phase are determined, how an increase in Cdk activity generates directionality in the cell cycle, and why cell cycle transitions are abrupt rather than gradual. These considerations lead to a general quantitative model of cell cycle control, in which opposing kinase and phosphatase activities have an essential role in ensuring dynamic transitions.

PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase

“…Another critical task at G2/M is to completely terminate DNA replication. Aurora is a master G2/M phase kinase 28 , and PP2A phosphatase counteracts ATM and ATR functions in DNA damage 54 . Here we demonstrate that both PP2A phosphatase and Aurora kinase promote the termination of telomere replication through modifications on Cdc13.…”

“…G2/M is the stage to terminate DNA replication and execute cell division. CDK, Aurora and Polo-like kinases are three major kinases to coordinate G2/M phase progression 28 . Aurora kinases are master controllers that manage multiple processes during cell division 29 .…”

Synergistic inhibition of colon cancer cell growth by a combination of atorvastatin and phloretin

“…Specifically, cdc2 kinase activation is the pivotal regulator mechanism responsible for the G 2 /M checkpoint. Activation of cdc2 is controlled via two steps: One is cyclin binding; the other is the dephosphorylation of cdc2 at Tyr15, which is the core regulatory step (31).…”

Apoptosis and cell cycle

“…Сложени кон-тролни механизми обезбеђују напредовање циклуса у жељеном смеру и проверавају да ли су у одређеној фази испуњени сви неоп-ходни услови за прелазак у следећу фазу. У регулацији ћелијског циклуса важну улогу имају циклин зависне киназе и циклини, као и инхибитори циклин зависних киназа 14 . Циклин зависне киназе, Cdks (Cyclin dependent kinases) су група ензима чија актив-ност расте и опада у току ћелијског циклуса, регулишући кључне догађаје у репликацији генетичког материјала и ћелијској деоби.…”

“…Complex control mechanisms provide the cycle progression in a desirable direction and checkwhether all necessary conditions for the transition into the next phase are fulfilled.Important role in the cell cycle regulation have cyclin dependent kinases and cyclins, as well as cyclin dependent kinase inhibitors 14 .…”