Date of Award

1-1-2016

Document Type

Dissertation

Degree Name

Ph.D.

Department

Biological Sciences

First Advisor

Scott A. Barbee, Ph.D.

Keywords

Genetic factors, Protein homeostasis, p38Kb-dependent proteins, Charcot-Marie-Tooth disease, Limb-girdle muscular dystrophy

Abstract

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.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Provenance

Received from ProQuest

Rights holder

Sarah Mae Ryan

File size

144 p.

File format

application/pdf

Language

en

Discipline

Biology

Included in

Biology Commons

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