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Yeast Cip1 is activated by environmental stress to inhibit Cdk1-G1 cyclins via Mcm1 and Msn2/4.
Upon environmental changes, proliferating cells delay cell cycle to prevent further damage accumulation. Yeast Cip1 is a Cdk1 and Cln2-associated protein. However, the function and regulation of Cip1 are still poorly understood. Here we report that Cip1 expression is co-regulated by the cell-cycle-mediated factor Mcm1 and the stress-mediated factors Msn2/4. Overexpression of Cip1 arrests cell cycle through inhibition of Cdk1-G1 cyclin complexes at G1 stage and the stress-activated protein kinase-dependent Cip1 T65, T69, and T73 phosphorylation may strengthen the Cip1and Cdk1-G1 cyclin interaction. Cip1 accumulation mainly targets Cdk1-Cln3 complex to prevent Whi5 phosphorylation and inhibit early G1 progression. Under osmotic stress, Cip1 expression triggers transient G1 delay which plays a functionally redundant role with another hyperosmolar activated CKI, Sic1. These findings indicate that Cip1 functions similarly to mammalian p21 as a stress-induced CDK inhibitor to decelerate cell cycle through G1 cyclins to cope with environmental stresses.A G1 cell cycle regulatory kinase Cip1 has been identified in budding yeast but how this is regulated is unclear. Here the authors identify cell cycle (Mcm1) and stress-mediated (Msn 2/4) transcription factors as regulating Cip1, causing stress induced CDK inhibition and delay in cell cycle progression.
Authors : Chang Ya-Lan , Tseng Shun-Fu , Huang Yu-Ching , Shen Zih-Jie , Hsu Pang-Hung , Hsieh Meng-Hsun , Yang Chia-Wei , Tognetti Silvia , Canal Berta , Subirana Laia , Wang Chien-Wei , Chen Hsiao-Tan , Lin Chi-Ying , Posas Francesc , Teng Shu-Chun ,
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Pathways :
WP510: MAPK Signaling Pathway
WP1019: FAS pathway and Stress induction of HSP regulation
WP1050: Oxidative Stress
WP1078: G1 to S cell cycle control
WP1138: FAS pathway and Stress induction of HSP regulation
WP1166: Oxidative Stress
WP1372: Oxidative Stress
WP1527: stress response
WP1530: miRNA regulation of DNA Damage Response
WP1579: DNA damage response
WP173: Oxidative Stress
WP1929: Thrombin signalling through proteinase activated receptors (PARs)
WP2038: Regulation of Microtubule Cytoskeleton
WP2087: miRNA regulation of DNA Damage Response
WP2137: Prenatal Stress & BDNF
WP2199: Seed Development
WP2431: Spinal Cord Injury
WP2432: Spinal Cord Injury
WP2433: Spinal Cord Injury
WP314: FAS pathway and Stress induction of HSP regulation
WP348: G1 to S cell cycle control
WP408: Oxidative Stress
WP412: Oxidative Stress
WP45: G1 to S cell cycle control
WP511: FAS pathway and Stress induction of HSP regulation
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Bibliography :
[28676626] Yeast Cip1 is activated by environmental stress to inhibit Cdk1-G1 cyclins via Mcm1 and Msn2/4.
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