Hch1p Acts Differently From Its Homologue, Aha1p, in Regulating Sensitivity of Hsp90 to Hsp90 Inhibitors in Yeast

• Author / Creator

  Armstrong, Heather K

• Hsp90 is a molecular chaperone that plays a vital role in the regulation of oncoproteins, is targeted by small molecule Hsp90-inhibitors in cancer studies, and is functionally regulated by a cohort of proteins called co-chaperones.
  We determined that deletion of the co-chaperone Hch1p, but not its homologue Aha1p, restores growth in yeast expressing the temperature-sensitive Hsp90 mutants, Hsp82pA587T or Hsp82pG313S. Strains expressing either of these Hsp90 mutants are hypersensitive to Hsp90 inhibitors. Sensitivity is reversed when HCH1 is deleted. Over-expression of HCH1 confers hypersensitivity to Hsp90 inhibitors in wild-type yeast, and HCH1 deletion confers high resistance to these drugs. We also determined that Hch1p, but not Aha1p, is essential for growth of yeast expressing the temperature-sensitive mutant, Hsp82pE381K. We conclude that the co-chaperone Hch1p plays an important role in regulating sensitivity to drugs that inhibit Hsp90 and regulates Hsp90 in a manner distinct from its homologue, Aha1p.

• Subjects / Keywords

  • Hch1
  • E381K
  • A587T
  • G313S
  • Aha1
  • Hsp90

• Graduation date

  Spring 2013

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3TC7R

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.