Date of Award
Scott A. Barbee, Ph.D.
Genetic Factors, Protein Homeostasis, p38Kb-Dependent Proteins, Charcot-Marie-Tooth Disease, Limb-Girdle Muscular Dystrophy
Aging is characterized by a failure to maintain proper protein homeostasis, potentially leading to tissue dysfunction. Though a variety of genes have been found to regulate lifespan and age-related behaviors how these genetic factors contribute to protein homeostasis has not been fully explored. Here, we report that the evolutionarily conserved aging gene p38 MAPK (p38Kb) regulates age-dependent protein homeostasis. Over-expression of p38Kb results in reduced protein aggregation, while knockout of p38Kb leads to increased protein aggregation. Furthermore, we find that p38Kb regulates protein homeostasis, lifespan, and age-dependent locomotor functions through an interaction with the Chaperone Assisted Selective Autophagy complex; a protein quality control mechanism that selectively degrades misfolded or damaged proteins. We also find that p38Kb regulates the expression of a number of proteins linked to cytoskeletal and neuronal function. Many of these p38Kb-dependent proteins are linked to the human neuropathy Charcot-Marie-Tooth disease and Limb-Girdle Muscular Dystrophy.
Ryan, Sarah Mae, "The Role of p38 MAPK in Protein Homeostasis and Aging" (2016). Electronic Theses and Dissertations. 1179.
Received from ProQuest
Sarah Mae Ryan