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P 10 - Prof. Dr. Sabine Rospert
Function of the Hsp70 homolog Ssb in the maintenance of cellular energy homeostasis
Prof. Dr. Sabine Rospert Institut für Biochemie und Molekularbiologie II Stefan-Meier-Str. 17 79104 Freiburg Phone: +49 761 203-5259 Fax: +49 761 203-5257 | |
Project Summary
The major signal regulating growth of yeast is the fluctuating nutrient content of the environment. SNF1, the homolog of the mammalian AMP-activated kinase (AMPK), is the major kinase responsible for adaptation to glucose limitation. When glucose is available, SNF1 is dephosphorylated and inactive. Dephosphorylation of SNF1 requires the essential phosphatase Glc7, the Glc7 targeting subunit Reg1, and Ssb, a chaperone of the Hsp70 family. Ssb can bind to ribosomes and nascent chains, and serves multiple functions in the cell. We found that Glc7 can dephosphorylate SNF1 in the absence of Reg1 only, if Ssb or the 14-3-3 protein Bmh is overexpressed. Crosslinking experiments revealed that in the cell, Ssb, Bmh, SNF1, and Glc7/Reg1 form an interacting network. 14-3-3 proteins are essential components of multiple signaling pathways. In many respects 14-3-3 proteins resemble molecular chaperones with the characteristic that binding to client proteins is regulated via phosphorylation. Our results provide an explanation of how Ssb can affect SNF1/Glc7 signaling. We now wish to investigate the functional and physical interplay between Bmh, Ssb, and their client proteins on a mechanistic level. Based on our data and on work published by others, we aim to analyze the role of Ssb, Bmh, and the Hsp70 homolog Rtg2, in the retrograde response and Hsf1 (heat shock transcription factor) signaling pathways. We will also follow up on our finding that Ssb is required for the shut-down of translation upon acute glucose depletion. We aim to test if Ssb, by its ability to physically interact with components of nutrient-sensing signaling pathways and the ribosome, affects the regulatory phosphorylation of components of the translational machinery. The results of these investigations shall further our understanding of how a eukaryotic cell responds to changes in its environment. | |