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.

Copyright Date

January 2016

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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