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標題: | 壓力環境下Mcm1和Msn2/4調控酵母菌Cip1對細胞週期之抑制 Yeast Cip1 is activated by environmental stress to inhibit Cdk1-G1 cyclins via Mcm1 and Msn2/4 |
作者: | Ya-Lan Chang 張雅嵐 |
指導教授: | 鄧述諄(Shu-Chun Teng) |
關鍵字: | 細胞週期,滲透壓力,磷酸化, cell cycle,osmotic stress,phosphorylation,CKI,Cdk1,Mcm1,Msn2/4,p21,p53, |
出版年 : | 2017 |
學位: | 博士 |
摘要: | 在環境變化之下,增生中的細胞延緩細胞週期以防止進一步的損傷積累。酵母菌的Cip1蛋白已知與Cdk1和Cln2具有交互作用;然而Cip1的功能和調控目前還仍有許多的未知。在本篇論文中,Cip1的表現由細胞週期調控因子Mcm1和壓力調控因子Msn2/4所共同調節。過表現Cip1透過抑制G1時期的Cdk1-G1細胞週期蛋白複合物,且在滲透壓壓力刺激下的Cip1蛋白T65、T69和T73磷酸化可以增強Cip1蛋白和Cdk1-G1細胞週期蛋白複合物的相互作用,從而抑制細胞週期。Cip1蛋白的主要抑制目標為Cdk1-Cln3複合物,從而阻止Whi5蛋白的磷酸化並抑制早期G1時期的進行。在滲透壓力下,Cip1的表現引發暫時性的G1時期延遲,而這與另一種被高滲透壓活化的CKI,Sic1蛋白在功能上是冗餘的。這些研究結果顯示,Cip1蛋白的功能類似於哺乳動物p21蛋白,皆作為壓力誘導的CDK抑制物,藉由抑制G1時期來減緩細胞週期,以利細胞應對外在環境的壓力。 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 Cip1 and 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 similar to mammalian p21 as a stress induced CDK inhibitor to decelerate cell cycle through G1 cyclins to cope with environmental stresses. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67612 |
DOI: | 10.6342/NTU201702171 |
全文授權: | 有償授權 |
顯示於系所單位: | 微生物學科所 |
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