REGULATION OF THE TRANSCRIPTION FACTOR MET4

这个子项目是众多研究子项目之一

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.