A Feedback Circuit between Transcriptional Activation and Self-Destruction of Gcn4 Separates Its Metabolic and Morphogenic Response in Diploid Yeasts
详细信息    查看全文
文摘
The basic zipper Gcn4 protein activates transcription in the yeast Saccharomyces cerevisiae in response to amino acid starvation. This includes numerous metabolic genes of amino acid or purine biosynthesis and the developmental cell-surface flocculin gene FLO11, which is required for diploid pseudohyphae formation and for adhesion upon nutrient starvation. We separated the metabolic from the developmental response by screening for GCN4 alleles that allow growth during amino acid starvation but are impaired in adhesion and are unable to form pseudohyphae. The identified Gcn4L267S variant carries an amino acid substitution in the third of the four conserved leucines of the zipper dimerization domain. This mutation abolished FLO11 expression and results in reduced but sufficient transcriptional activity for amino acid biosynthetic genes. The Leu267Ser substitution impairs Gcn4 homodimer formation and is a significantly more stable protein than the wild-type protein. A helix-breaker substitution in Leu253 results in a transcriptionally inactive but highly stable protein variant. This is due to a feedback circuit between transcriptional activity of Gcn4 and its own stability, which depends on the Gcn4-controlled cyclin PCL5. Gcn4L253G reduces the expression of Pcl5 and therefore reduces its own degradation. This self-controlled buffer system to restrict transcriptional activity results in a reciprocal correlation between Gcn4 transcriptional activity and protein stability.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700