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Journal of Undergraduate Research

Keywords

PAS kinase, Cbf1 in cellular metabolism, obese, metabolism functions

College

Life Sciences

Department

Microbiology and Molecular Biology

Abstract

The most recent National Institute of Health report concludes that 68.8% of American adults are considered to be overweight or obese1. With this trend in obesity, metabolic diseases such as heart disease, stroke, cancer, and diabetes are on the rise. The critical yet basic function of cellular homeostasis is a central component in controlling these diseases. Sensory protein kinases are essential in the phosphorylation of many protein substrates, allowing them to control several metabolic functions and appropriately allocate glucose, maintaining homeostasis in cells. PAS kinase is a sensory protein kinase that is highly conserved and plays a crucial role in cellular respiration. Although PAS kinase is a necessary component for essential metabolic functions, little is known about the molecular mechanisms behind these functions. We have recently discovered a key substrate of PAS kinase that affects glucose metabolism in the cell, Centromere binding factor 1 (Cbf1)2. Cbf1 regulates genes involved in respiration, and we have shown that the phosphorylation of Cbf1 by PAS kinase inhibits Cbf1, decreasing respiration in yeast cells. In agreement, when PAS kinase is knocked out of cells, there is a significant Cbf1-dependent increases in cellular respiration rates. Cbf1’s importance is further supplemented by its human homolog, USF1, which has been associated with hyperlipidemia in humans. We have recently shown that USF1, like its yeast homolog, rescues cellular respiration as well.

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