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Published on: July 30, 2014
通过Far1直接抑制酵母循环素依赖激酶Cdc28-Cln的直接抑制
1Department of Biochemistry and Biophysics, University of California at San Francisco 94143-0448.
概括
抗菌原α因子通过激活抑制Cdc28-Cln激酶的途径,触发了Saccharomyces cerevisiae中的细胞循环停止. 对于这种停止,Far1蛋白质是必不可少的,它直接抑制了Cdc28-Cln激酶的活性.
科学领域:
- * 分子和细胞生物学
- * 酵母遗传学公司
- * * 信号转导 信号转导
背景情况:
- *Saccharomyces cerevisiae利用信号传导途径在G1阶段停止细胞周期,以应对像α因子这样的抗菌原体.
- *这种捕获机制涉及抑制特定的循环素依赖激酶,这些激酶是细胞循环进展的关键调节者.
- * Far1蛋白已被确定为这种细胞反应途径的关键组成部分.
研究的目的:
- *阐明Far1蛋白在Saccharomyces cerevisiae中的α因子诱导的G1细胞周期停止中的精确作用.
- * 为了研究Far1通过哪种机制来调解林依赖性激酶Cdc28-Cln.的抑制.
- * 为了确认Far1的功能作为阿尔法因子信号级联中的最终效应器.
主要方法:
- * 通过使用α因子治疗,研究了Saccharomyces cerevisiae中的细胞循环停止.
- *分析了Far1蛋白与Cdc28-Cln复合物的关联.
- * 进行了体内和体外激酶试验,以评估Far1对Cdc28-Cln活性的抑制作用.
主要成果:
- *在Saccharomyces cerevisiae的G1阶段通过α因子阻止细胞循环,需要Far1蛋白的存在.
- * Far1 蛋白直接与 Cdc28-Cln 复合体结合.
- *Cdc28-Cln的激酶活性被Far1抑制,无论是在细胞内 (体内) 还是在纯化的系统中 (体外).
结论:
- *Far1对于Saccharomyces cerevisiae中α因子诱导的G1细胞周期停止至关重要.
- * Far1 功能位于阿尔法因子响应路径的终端阶段.
- *Far1直接抑制G1循环素依赖的激酶活性,特别是Cdc28-Cln,以调解细胞循环停止.
相关概念视频
Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Inhibition of CDK Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...

