Sic2為一酵母菌逆境誘發之G1時期細胞週期磷酸酶抑制物

Abstract

為了在自然界中生存，酵母細胞必須針對瞬息萬變的外在壓力做出快速並且適當的反應。細胞當細胞遭遇環境壓力，例如滲透壓壓力時，細胞週期會停頓在G1時期，讓細胞適應並且排除壓力。細胞週期中G1到S期的轉換是由G1週期素和Cdc28週期素依賴性蛋白激酶複合體的活性來調控。G1週期素中的Cln1和Cln2對於細胞週期的啟動提供了特殊的貢獻，而Cln3則是作用在CLN1和CLN2時間點之上的表現和其他在G1時期表現的基因。之前的研究顯示出Ypl014w (我們命名為Sic2)是Cdc28/G1週期素複合體的其中一員。然而，這個基因是如何在細胞週期中被調控，以及是否影響週期素依賴性蛋白激酶素–G1週期素複合體的活性仍然是未知的。在本篇論文中，我們發現SIC2會在細胞遭遇逆境時被轉錄因子Mns2/4表現，或是隨者細胞週期中受到轉錄因子Mcm1的調控。當Sic2大量表現時，細胞週期大規模地停滯在G1時期。利用共同免疫沉澱法證實了Sic2和G1週期素是會互相結合的。此外，Sic2對於滲透壓力造成的暫時性G1週期停頓有重要的貢獻，其功能在此逆境情況下與Sic1有重複性。本篇論文證明Sic2可能是週期素依賴性蛋白激酶的抑制物，且在細胞遭受逆境時調控細胞週期的進行。

To survive, budding yeast Saccharomyces cerevisiae delays G1 progression under several stresses, such as osmotic stress, to prevent damage accumulation. The G1-S transition is controlled by the activity of Cdk1/G1 cyclin. Proteomic screening suggested that Sic2 is a component of the Cdk1/G1 cyclin complex. However, the regulation of Sic2 expression or its functions on the activity of the Cdk1/G1 cycling complex is still unknown. Here we demonstrated that expression of Sic2 is not only regulated through stress mediated transcriptional factor Msn2/4, but also by cell cycle mediated transcriptional factor Mcm1. Overexpression of Sic2 causes cyclin-mediated-cell cycle arrest at G1 stage, and this cell cycle inhibition of Sic2 is dependent on osmotic stress-induced T65, T69, T73 and S192 phosphorylation. The phosphorylation of Sic2 is required for its Cln3 interaction, which may cause the reduction of Cdk1/Cln3 activity by the competition with the Cdk1-Cln3 interaction. Under osmotic stress, we found that Sic2 can cause transient G1 delay and play as a functional redundant protein of major stress-induced CKI, Sic1. Our study implies that Sic2 serves as a CDK inhibitor to modulate cell cycle progression under environmental stresses.