Abstract
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.
Highlights
Upon environmental changes, proliferating cells delay cell cycle to prevent further damage accumulation
Simultaneous induction of one of G1 cyclins in the Cip[1] overexpressed strain partially rescued the Cip1-dependent slow growth through preventing G1 arrest (Fig. 1d). These results suggest that Cip1-mediated G1 arrest is due to the inhibitory targeting of Cip[1] to Cdk1–G1 cyclin complexes and this arrest can be rescued by increasing G1 cyclin expression
To further determine whether Cip[1] is a direct inhibitor of all three Cdk1–G1 cyclin complexes, we examined whether Cip[1] could inhibit the kinase activity of all three Cdk1–G1 cyclins purified from yeast extracts
Summary
Upon environmental changes, proliferating cells delay cell cycle to prevent further damage accumulation. Cip[1] expression triggers transient G1 delay which plays a functionally redundant role with another hyperosmolar activated CKI, Sic[1]. These findings indicate that Cip[1] functions to mammalian p21 as a stress-induced CDK inhibitor to decelerate cell cycle through G1 cyclins to cope with environmental stresses. Mcm[1] is required for pheromone response and regulates the transcription of multiple cell-cycle genes[27,28,29]. Deletion of the ECBs from CLN3 and SWI4 promoters reduces their expression and causes a G1–S delay[30]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
