Characterizing the Function of PAS kinase in Cellular Metabolism and Neurodegenerative Disease

• Main Author: Pape, Jenny Adele
• Format: Others
• Published: BYU ScholarsArchive 2019
• Subjects: PAS kinase; Cbf1; USF1; respiration; glucose allocation; ALS; neurodegenerative; ataxin-2; Pbp1; stress granules; Ptc6; mitophagy
• Online Access: https://scholarsarchive.byu.edu/etd/8552; https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=9552&context=etd

The second identified substrate of PAS kinase discussed is Pbp1. The human homolog of Pbp1 is ataxin-2, mutations in which are a known risk factor for amyotrophic lateral sclerosis (ALS). As diet and sex have been shown to be important factors regarding PAS kinase function, they also are strong contributing factors to ALS and are extensively reviewed herein. Pbp1 is known to be sequestered by PAS kinase under glucose depravation, and it can sequester additional proteins along with it to regulate different cellular pathways. To shed light on the pathways affected by Pbp1, we performed a yeast two-hybrid assay and mass spectrometry, identifying 32 novel interacting partners of Pbp1 (ataxin-2). We provide further analysis of the direct binding partner Ptc6, measuring mitophagy, mitochondrial content, colocalization, and respiration. This work elucidates novel molecular mechanisms behind the function of PAS kinase and yields valuable insights into the role of PAS kinase in disease.