Inhibition of Yap2 activity by MAPKAP kinase Rck1 affects yeast tolerance to cadmium

Daiane Mazzola; Catarina Pimentel; Soraia Caetano; Catarina Amaral; Regina Menezes; Claudia N Santos; Elis Eleutherio; Claudina Rodrigues-Pousada

doi:10.1016/j.febslet.2015.07.049

Inhibition of Yap2 activity by MAPKAP kinase Rck1 affects yeast tolerance to cadmium

FEBS Lett. 2015 Sep 14;589(19 Pt B):2841-9. doi: 10.1016/j.febslet.2015.07.049. Epub 2015 Aug 18.

Authors

Daiane Mazzola¹, Catarina Pimentel², Soraia Caetano², Catarina Amaral², Regina Menezes³, Claudia N Santos⁴, Elis Eleutherio⁵, Claudina Rodrigues-Pousada⁶

Affiliations

¹ Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2781-901 Oeiras, Portugal; Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Avenida Athos da Silveira Ramos 149, Bloco A, Lab 547, Rio de Janeiro, RJ 21941-909, Brazil.
² Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2781-901 Oeiras, Portugal.
³ Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2781-901 Oeiras, Portugal; Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal.
⁴ Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal.
⁵ Department of Biochemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Avenida Athos da Silveira Ramos 149, Bloco A, Lab 547, Rio de Janeiro, RJ 21941-909, Brazil. Electronic address: eliscael@iq.ufrj.br.
⁶ Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, EAN, 2781-901 Oeiras, Portugal. Electronic address: claudina@itqb.unl.pt.

PMID: 26296316
DOI: 10.1016/j.febslet.2015.07.049

Abstract

Yap2 is a cadmium responsive transcription factor that interacts with MAPK-activated protein (MAPKAP) kinase Rck1. We show that Rck1 deletion confers protection against cadmium toxicity and that the mechanism underlying this observation relies on Yap2. Rck1 removal from the yeast genome potentiates Yap2 activity by increasing protein half-life and delaying its nuclear export. As a consequence, several Yap2 antioxidant targets are over-activated by a mechanism that also requires Yap1. Several genes of the cell wall integrity (CWI) pathway are upregulated under cadmium stress in a Yap2 dependent way. We showed that deletion of CWI genes renders yeast cells more sensitive to cadmium. These findings led us to suggest that in response to cadmium stress Yap2 may serve a dual purpose: oxidative stress attenuation and cell wall maintenance.

Keywords: Cadmium; MAPK-activated protein; Rck1; Yap2; Yeast.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus / drug effects
Antioxidants / metabolism
Cadmium / toxicity*
Cell Nucleus / drug effects
Cell Nucleus / metabolism
Cell Wall / drug effects
Cell Wall / genetics
Environmental Pollutants / toxicity*
Gene Expression Regulation, Fungal / drug effects
Mutation
Oxidative Stress / drug effects
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Protein Stability / drug effects
Saccharomyces cerevisiae / cytology
Saccharomyces cerevisiae / drug effects*
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae / physiology
Saccharomyces cerevisiae Proteins / antagonists & inhibitors*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Transcription Factors / antagonists & inhibitors*
Transcription Factors / metabolism*

Substances

Antioxidants
CAD1 protein, S cerevisiae
Environmental Pollutants
Saccharomyces cerevisiae Proteins
Transcription Factors
Cadmium
Protein Serine-Threonine Kinases
RCK1 protein, S cerevisiae