Calcineurin inhibitors suppress the high-temperature stress sensitivity of the yeast ubiquitin ligase Rsp5 mutant: a new method of screening for calcineurin inhibitors

• DOI: 10.1111/1567-1364.12143
• Publication Date: 2014-02-13T08:29:51Z
• Authors: Shota Uesugi; Daisuke Watanabe; Moe Kitajima; Ryo Watanabe; Yumi Kawamura; Motoko Ohnishi; Hiroshi Takagi; Ken-ichi Kimura
• Keywords: 0303 health sciences; Hot Temperature; Saccharomyces cerevisiae Proteins; Endosomal Sorting Complexes Required for Transport; Calcineurin Inhibitors; Drug Evaluation, Preclinical; Ubiquitin-Protein Ligase Complexes; Saccharomyces cerevisiae; Tacrolimus; Protein Phosphatase 2C; 03 medical and health sciences; Cyclosporine; Phosphoprotein Phosphatases

The ubiquitin/proteasome system plays significant and important roles in the regulation of metabolism various proteins. dysfunction this is involved several diseases, for example, cancer, neurogenic diseases chronic inflammation. Therefore, compounds, which regulate system, might be candidates development use as clinical drugs. Saccharomyces cerevisiae mutant (rsp5(A401E)) has a single amino acid change, Ala401Glu, RSP5 gene, encodes an essential E3 ubiquitin ligase, hypersensitive to high-temperature stress. Here, we found that immunosuppressants FK506 cyclosporin A, both known calcineurin inhibitors, complemented stress-induced growth defect rsp5(A401E) strain. pathway by disrupting CNB1 CRZ1 gene also partially stress sensitivity cells. Thus, these results suggest inhibition confers tolerance on Furthermore, some diterpenoid restore cells, showed activities protein phosphatase 2C activation. These indicate inhibitors suppress cells analysis their physiological function effective screening yeast