Date of Award

1-1-2016

Document Type

Dissertation

Degree Name

Ph.D.

Organizational Unit

Biological Sciences

First Advisor

Scott A. Barbee, Ph.D.

Second Advisor

Alysia Vrailas-Mortimer

Third Advisor

Joseph Angleson

Fourth Advisor

Dinah Loerke

Fifth Advisor

David Patterson

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.

Rights Holder

Sarah Mae Ryan

Provenance

Received from ProQuest

File Format

application/pdf

Language

en

File Size

144 p.

Discipline

Biology

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