REGULATION OF THE TRANSCRIPTION FACTOR MET4

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 酵母转录激活因子Met 4协调含硫化合物与细胞增殖的稳态。在正常生长条件下，Met 4维持在非活性状态，但当细胞内S-腺苷甲硫氨酸水平不足时，或细胞经历镉或砷胁迫时，Met 4迅速活化。Met 4控制转录程序，恢复S-腺苷甲硫氨酸水平，防止镉和砷胁迫引起的细胞损伤，并诱导细胞周期停滞。 Met 4的失活是通过多聚泛素化的蛋白水解独立调节实现的。泛素连接酶SCF-Met 30将Met 4保持在泛素化的无活性形式。抑制SCF-Met 30与Met 4去泛素化的组合快速激活Met 4以响应各种信号。 我们建议使用荧光显微镜来分析完整细胞中的Met 4活化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The yeast transcriptional activator Met4 coordinates homeostasis of sulfur-containing compounds with cell proliferation. Under normal growth conditions Met4 is maintained in an inactive state, but when the intracellular levels of S-adenosylmethionine are inadequate, or cells experience cadmium or arsenic stress, Met4 gets rapidly activated. Met4 controls a transcriptional program that restores S-adenosylmethionine levels, prevents cell damage by cadmium and arsenic stress, and induces a cell cycle arrest. Inactivation of Met4 is achieved by proteolysis-independent regulation by polyubiquitination. The ubiquitin ligase SCF-Met30 keeps Met4 in the ubiquitinated, inactive form. Inhibition of SCF-Met30 combined with Met4 deubiquitination rapidly activates Met4 in response to a variety of signals. We propose to use fluorescence microscopy to analyze Met4 activation in intact cells.