Protein kinase Snf1 is involved in the proper regulation of the unfolded protein response in Saccharomyces cerevisiae.

Glc7 is the only catalytic subunit of the protein phosphatase type 1 in the yeast S. cerevisiae and, together with its regulatory subunits, is involved in many and essential processes. Analysis of the non-essential mutants in the regulatory subunits of Glc7 revealed that the lack of Reg1, and no other subunit, causes hypersensitivity to unfolded-protein-response (UPR)-inducers, which was concomitant with an augmented UPR element-dependent transcriptional response. Glc7-Reg1complex takes part in the regulation of the yeast AMP-activated serine/threonine protein kinase Snf1 in response to glucose. We demonstrate here that the observed phenotypes of reg1 mutant cells are attributable to the inappropriate activation of Snf1. Indeed, growth in the presence of limited concentrations of glucose, where Snf1 is active, or expression of active forms of Snf1 in a wild-type strain, increased the sensitivity to the UPR-inducer tunicamycin. Furthermore, reg1 mutant cells showed a sustained HAC1 mRNA splicing and KAR2 mRNA levels during the recovery phase of the UPR, and dysregulation of the Ire1-oligomeric equilibrium. Finally, overexpression of protein phosphatases PTC2 and PTC3 alleviated the growth defect of reg1cells under endoplasmic reticulum (ER) stress conditions. Altogether, our results reveal that Snf1 plays an important role in the attenuation of the UPR, as well as identifying the protein kinase and its effectors as possible pharmacological targets for human diseases that are a...

Source: BJ Signal - March 2, 2015 Category: Biochemistry Authors: J Ferrer-dalmau, F Randez-Gil, M Marquina, J A Prieto, A Casamayor Tags: BJ Signal Source Type: research