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.

Copyright Statement / License for Reuse

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Provenance

Received from ProQuest

Rights holder

Sarah Mae Ryan

File size

144 p.

File format

application/pdf

Language

en

Discipline

Biology

Available for download on Friday, September 14, 2018

Included in

Biology Commons

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