Thesis advisor: Charles Hoffman / The fission yeast Schizosaccharomyces pombe senses environmental glucose through a cAMP-signaling pathway. Elevated cAMP levels activate protein kinase A (PKA) to inhibit transcription of genes involved in sexual development and gluconeogenesis, including the fbp1⁺ gene, which encodes fructose-1,6-bisphosphatase. Glucose-mediated activation of PKA requires the function of nine git genes (git=glucose insensitive transcription), encoding adenylate cyclase, the PKA catalytic subunit and seven “upstream” proteins required for glucose-triggered adenylate cyclase activation. This thesis describes the cloning and characterization of the git10⁺ gene, which is identical to swo1⁺ and encodes the S. pombe Hsp90 chaperone protein. This discovery is consistent with the previous identification of the Git7 protein as a member of the Sgt1 Hsp90 co-chaperone family. Glucose repression of fbp1⁺ transcription is impaired by both hsp90⁻ and git7⁻ mutant alleles, as well as by chemical inhibition of Hsp90 activity and temperature stress. Unlike the swo1⁻ and git7⁻ ts mutant alleles, the git10-201 allele and git7-93 allele support cell growth at 37º and show no cytokinesis defect, while severely reducing glucose repression of an fbp1-lacZ reporter, suggesting a separation-of-function defect. A physical interaction between Git7 and Hsp90 in S. pombe was also detected and findings in this thesis suggest their involvement in the initial assembly of the cAMP complex. / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.
| Identifer | oai:union.ndltd.org:BOSTON/oai:dlib.bc.edu:bc-ir_101320 |
| Date | January 2008 |
| Creators | Alaamery, Manal |
| Publisher | Boston College |
| Source Sets | Boston College |
| Language | English |
| Detected Language | English |
| Type | Text, thesis |
| Format | electronic, application/pdf |
| Rights | Copyright is held by the author, with all rights reserved, unless otherwise noted. |
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