Valdivieso M H, Sugimoto K, Jahng K Y, Fernandes P M, Wittenberg C
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037.
Mol Cell Biol. 1993 Feb;13(2):1013-22. doi: 10.1128/mcb.13.2.1013-1022.1993.
Yeast cells arrest during the G1 interval of the cell cycle in response to peptide mating pheromones. The FAR1 gene is required for cell cycle arrest but not for a number of other aspects of the pheromone response. Genetic evidence suggests that FAR1 is required specifically for inactivation of the G1 cyclin CLN2. From these observations, the FAR1 gene has been proposed to encode an element of the interface between the mating pheromone signal transduction pathway and the cell cycle regulatory apparatus. We show here that FAR1 is necessary for the decrease in CLN1 and CLN2 transcript accumulation observed in response to mating pheromone but is unnecessary for regulation of the same transcripts during vegetative growth. However, the defect in regulation of CLN1 expression is dependent upon CLN2. We show that pheromone regulates the abundance of Cln2 at a posttranscriptional level and that FAR1 is required for that regulation. From these observations, we suggest that FAR1 function is limited to posttranscriptional regulation of CLN2 expression by mating pheromone. The failure of mating pheromone to repress CLN2 transcript levels in far1 mutants can be explained by the stimulatory effect of the persistent Cln2 protein on CLN2 transcription via the CLN/CDC28-dependent feedback pathway.
酵母细胞在细胞周期的G1期因肽类交配信息素而停滞。FAR1基因是细胞周期停滞所必需的,但对于信息素反应的许多其他方面并非必需。遗传学证据表明,FAR1专门用于使G1细胞周期蛋白CLN2失活。基于这些观察结果,有人提出FAR1基因编码交配信息素信号转导途径与细胞周期调节装置之间界面的一个元件。我们在此表明,FAR1对于响应交配信息素时观察到的CLN1和CLN2转录物积累的减少是必需的,但对于营养生长期间相同转录物的调节并非必需。然而,CLN1表达调节中的缺陷取决于CLN2。我们表明,信息素在转录后水平调节Cln2的丰度,并且FAR1是该调节所必需的。基于这些观察结果,我们认为FAR1的功能仅限于通过交配信息素对CLN2表达进行转录后调节。在far1突变体中交配信息素未能抑制CLN2转录水平,可以通过持续的Cln2蛋白通过CLN/CDC28依赖性反馈途径对CLN2转录的刺激作用来解释。