蛋白質Rsp5和Pph3 調控磷酸化之蛋白質Cdc13及其訊息傳遞

Rsp5 and Pph3 switch off the signals of phosphorylation of Cdc13

沈子傑(Zih-Jie Shen)

指導教授 ： 鄧述諄

國立臺灣大學/醫學院/微生物學研究所/碩士(2009年)

https://doi.org/10.6342/NTU.2009.01813

摘要

在酵母菌 Saccharomyces cerevisiae中，端粒體蛋白質Cdc13 的功能在於藉由延攬端粒酶延長端立體以及保護染色體末端結構。 在整個細胞分裂的過程中，蛋白質Cdc13 的表現量以及被磷酸化的程度從G1時期往G2/M 時期達到最高峰，而在繼續往G1時期會逐漸減少。在先前的研究指出，蛋白質Rsp5參與裂解單股DNA結合蛋白質Rpa1。而且，Cdc13和Rpa1的結構相類似。因此推測Cdc13的裂解可能經由蛋白質Rsp5所調控。此外，蛋白質Cdc13和Rad53都被DNA損傷反應蛋白激酶Mec1所磷酸化。 而且，Rad53的去磷酸化經由蛋白質Ptc2/Ptc3和Pph3所完成。在本篇研究中，我發現蛋白質Pph3在生體內(in vivo)調控Cdc13的去磷酸化。總結，這兩項發現可推測端粒酶延長端粒體長度的功能可能經由Rsp5 和Pph3對於Cdc13的表現量降低及去磷酸化程度來終止。

關鍵字

端粒體 ； 蛋白質裂解 ； 去磷酸化

並列摘要

In Saccharomyces cerevisiae, the telomere binding protein Cdc13 activates telomere replication by recruiting telomerase, and also performs an essential function in chromosome end protection. Through cell cycle progression, the protein expression level and phosphorylated status of Cdc13 is highest in G2/M phase and decreases in G1 phase. In previous studies, Rsp5 is involved in the degradation of the ssDNA binding protein, Rpa1. Since Cdc13 and Rpa1 share a similar domain organization, I speculate that Cdc13p level is regulated through proteasome-dependent degradation. I found that Rsp5 is a specific ubiquitin E3 ligase of Cdc13. Moreover, Cdc13 and Rad53 are both phosphorylated by the DNA damage-responsive protein kinase, Mec1. Rad53 dephosphorylation has been shown to be dependent on the presence of the PP2C-like phosphatase Ptc2/Ptc3 and PPh3. I found that Pph3 mediates Cdc13 dephosphorylation from G2/M to G1 phase. Take together; these findings suggest that both proteins degradation and dephosphorylation promote telomerase inactivation at the M phase. When cells need to stop telomere replication and enter the next stage of cell cycle.

並列關鍵字

telomere ； proteolysis ； dephosphorylation

參考文獻

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