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Akt Phosphorylation of Drosophila Heat-Shock Factor: A Signature for Stress Resistance

Citation

Mohanty, Sarina (2008) Akt Phosphorylation of Drosophila Heat-Shock Factor: A Signature for Stress Resistance. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9CV4FQJ. https://resolver.caltech.edu/CaltechETD:etd-05302008-150414

Abstract

The heat-shock response is vital to cellular homeostasis. Drosophila melanogaster heat-shock factor (dHSF) is the primary transcriptional activator in the stress response pathway for induction of heat-shock-mediated gene transcription. This work investigates the potential for dHSF to undergo post-translational modification by phosphorylation and lysine tagging, specifically, direct phosphorylation by kinases and covalent-lysine tagging by ubiquitin, acetyl, and SUMO groups. Direct phosphorylation of, and binding to, dHSF was demonstrated by Akt/PKB kinase. Knock-down of this kinase by RNAi resulted in a heat-shock phenotype for dHSF and the acquired DNA-binding ability characteristic of activated transcription factor. Site-directed mutagenesis of lysines within a putative nuclear localization sequence (NLS) revealed two potential sites for regulation of dHSF activation by post-translational modification. The functional consequences of synergistic Akt phosphorylation and lysine modifications are discussed – this work implicates a role for direct kinase phosphorylation in regulating the stability of dHSF.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:heat-shock; kinase; transcription
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Biochemistry and Molecular Biophysics
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Parker, Carl Stevens
Thesis Committee:
  • Rees, Douglas C. (chair)
  • Parker, Carl Stevens
  • Sternberg, Paul W.
  • Dunphy, William G.
Defense Date:12 May 2008
Record Number:CaltechETD:etd-05302008-150414
Persistent URL:https://resolver.caltech.edu/CaltechETD:etd-05302008-150414
DOI:10.7907/Z9CV4FQJ
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:5218
Collection:CaltechTHESIS
Deposited By: Imported from ETD-db
Deposited On:02 Jun 2008
Last Modified:03 Oct 2019 23:42

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