Author(s): Ashley Jones
Mentor(s): Julianne Grose
Institution BYU
The NAD kinase plays a crucial role in cellular metabolism and growth, as it is the only known enzyme that phosphorylates NAD+ to form the cofactor NADP+. NADP+ (along with its reduced form NADPH) are required in over 300 reactions in the cell, primarily essential biosynthetic reactions as well as reactions necessary for oxidative stress repair. Recently, the Grose lab identified the metabolic regulator PAS kinase as an upstream protein kinase of NAD kinase (Utr1) in yeast. PAS kinase was previously known to play a pivotal role in lipid and glucose metabolism, however little of its substrates have been reported and characterized. Our research seeks to characterize the relationship between PAS kinase and its substrate NAD kinase, something that is not already established. My goal is to further characterize the effects of PAS kinase on Utr1, including the unique roles that Utr1 plays in yeast and how they are affected by phosphorylation. My key hypotheses are that: (1) Utr1 plays a unique role in the cell through localization and protein/protein interactions, handing off NADP to key pathways in the cell. (2) PAS kinase affects Utr1 by altering its binding partners and hence, the pathways for which NADP is used. Testing these hypotheses involves using yeast, a model organism. It will be done using yeast 2-hybridization assays and co-immunoprecipitation assay. Metabolic processes in yeast mirror processes in humans. Due to their pivotal roles in metabolism and oxidative repair, both PAS kinase and NAD kinase have been identified as therapeutic targets, meaning our results could have implications in diabetes, cancer, and obesity.