Schweitzer Kelly, Cocklin Ross, Garrett Lisa, Desai Falguni, Goebl Mark
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Yeast. 2005 May;22(7):553-64. doi: 10.1002/yea.1234.
The presence of the appropriate pheromone induces alpha and a cells of the yeast Saccharomyces cerevisiae to activate both changes in transcriptional expression and cell polarity that eventually lead to the mating of alpha and a cells to form a/alpha diploid cells. A third response after exposure to mating pheromone is a transient cell cycle arrest, allowing synchronization of the two cell types in G1 prior to cell fusion. At least in part, this cell cycle arrest requires the inactivation of Cln-kinase activity through transcriptional inactivation of the CLN1 and CLN2 genes, degradation of the Cln proteins and direct inhibition of Cln-kinase complexes. Here we report that GRR1, which encodes a substrate recognition subunit of SCF complexes, is critical for pheromone sensitivity and likely for this arrest. Loss of SCF(Grr1) function by deletion of the GRR1 gene causes pheromone resistance. However, deletion of CLN1 and CLN2 restores pheromone sensitivity to grr1Delta cells. Thus, rapid loss of Cln-kinase activity during mating may require coordinated inactivation of the Cln-kinase complexes, inactivation of CLN transcription and SCF(Grr1)-dependent Cln degradation.
合适信息素的存在会诱导酿酒酵母的α细胞和a细胞激活转录表达变化和细胞极性变化,最终导致α细胞和a细胞交配形成a/α二倍体细胞。暴露于交配信息素后的第三种反应是短暂的细胞周期停滞,使两种细胞类型在细胞融合前于G1期同步。至少部分而言,这种细胞周期停滞需要通过CLN1和CLN2基因的转录失活、Cln蛋白的降解以及对Cln激酶复合物的直接抑制来使Cln激酶活性失活。在此我们报告,编码SCF复合物底物识别亚基的GRR1对信息素敏感性至关重要,可能对这种停滞也很关键。通过缺失GRR1基因导致SCF(Grr1)功能丧失会引起信息素抗性。然而,缺失CLN1和CLN2可恢复grr1Δ细胞的信息素敏感性。因此,交配过程中Cln激酶活性的快速丧失可能需要Cln激酶复合物的协同失活、CLN转录的失活以及SCF(Grr1)依赖的Cln降解。