Pbp1 is a component of glucose deprivation induced stress granules and is involved in P-body-dependent granule assembly. We have recently shown that Pbp1 plays an important role in the interplay between three sensory protein kinases in yeast: AMP-regulated kinase (Snf1 in yeast), PAS kinase 1 (Psk1 in yeast), and the target of rapamycin complex 1 (TORC1), to regulate glucose allocation during nutrient depletion. This signaling cascade occurs through the SNF1-dependent phosphorylation and activation of Psk1, which phosphorylates and activates poly(A)- binding protein binding protein 1 (Pbp1), which then inhibits TORC1 through sequestration at stress granules. In this study we further characterized the regulation of Pbp1 by PAS kinase through the characterization of the role of the Psk1 homolog (Psk2) in Pbp1 regulation, and the identification of functional Pbp1 binding partners. Human ataxin-2 (ATXN2) is the homolog of yeast Pbp1 and has been shown to play an important role in the development of several ataxias. In this study we have also provided the evidence that human ataxin-2 can complement Pbp1 in yeast, and that human PAS kinase can phosphorylate human ataxin-2. Further characterizing this interplay between PAS kinase and Pbp1/ATXN2 aid in understanding pathways required for proper glucose allocation during nutrient depletion, including reducing cell growth and proliferation when energy is low. In addition, it yields valuable insights into the role of ataxin-2 in the development of devastating ataxias.
| Identifer | oai:union.ndltd.org:BGMYU2/oai:scholarsarchive.byu.edu:etd-7527 |
| Date | 01 September 2016 |
| Creators | Choksi, Nidhi Rajan |
| Publisher | BYU ScholarsArchive |
| Source Sets | Brigham Young University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | All Theses and Dissertations |
| Rights | http://lib.byu.edu/about/copyright/ |
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