Proteasomal Degradation of Rpn4

Wayne State University, Detroit MI

Investigators

Abstract

Proteasome-mediated protein degradation is a major regulatory mechanism in the cell. Recent studies from Dr. Xie's laboratory have shown that the proteasome homeostasis in the budding yeast Saccharomyces cerevisiae is regulated by a negative feedback circuit in which the transcription factor Rpn4 upregulates the proteasome genes and is rapidly degraded by the proteasome. In addition to the proteasome genes, Rpn4 controls the expression of numerous other genes, including a number of key stress response genes. Interestingly, the RPN4 gene itself is induced by a wide variety of environmental stresses. These observations indicate that Rpn4 serves as a hub in a stress response network onto which the environmental stimuli "fan in" and from which the response signals "fan out". The Rpn4-proteasome negative feedback circuit gauges the output signals by keeping the Rpn4 protein level in check and therefore is considered a core regulator of the Rpn4-mediated stress response network. The main focus of Dr. Xie's research is to elucidate the mechanisms underlying Rpn4 degradation. This is a crucial step to understand how the Rpn4-proteasome negative feedback circuit operates in response to environmental stress. Broader Impacts: This research will make a significant contribution to the training and education of students at various levels. Graduate and undergraduate students and high school students have participated in this study. More graduate students will be recruited to this research. Students will not only receive hands-on training of the powerful techniques of yeast genetics and molecular biology, but also learn how to ask and solve important biological questions. The information obtained from this study will directly benefit protection of the environment.