Role for RACK1 orthologue Cpc2 in the modulation of stress response in fission yeast.
The receptor of activated C kinase (RACK1) is a protein highly conserved among eukaryotes. In mammalian cells, RACK1 functions as an adaptor to favor protein kinase C (PKC)-mediated phosphorylation and subsequent activation of c-Jun NH(2)-terminal kinase mitogen-activated protein kinase. Cpc2, the RACK1 orthologue in the fission yeast Schizosaccharomyces pombe, is involved in the control of G2/M transition and interacts with Pck2, a PKC-type protein member of the cell integrity Pmk1 mitogen-activated protein kinase (MAPK) pathway. Both RACK1 and Cpc2 are structural components of the 40S ribosomal subunit, and recent data suggest that they might be involved in the control of translation. In this work, we present data supporting that Cpc2 negatively regulates the cell integrity transduction pathway by favoring translation of the tyrosine-phosphatases Pyp1 and Pyp2 that deactivate Pmk1. In addition, Cpc2 positively regulates the synthesis of the stress-responsive transcription factor Atf1 and the cytoplasmic catalase, a detoxificant enzyme induced by treatment with hydrogen peroxide. These results provide for the first time strong evidence that the RACK1-type Cpc2 protein controls from the ribosome the extent of the activation of MAPK cascades, the cellular defense against oxidative stress, and the progression of the cell cycle by regulating positively the translation of specific gene products involved in key biological processes.
Núñez
Andrés
A
Yeast Physiology Group, Department of Genetics and Microbiology, Facultad de Biología, University of Murcia, 30071 Murcia, Spain.
Franco
Alejandro
A
Madrid
Marisa
M
Soto
Teresa
T
Vicente
Jero
J
Gacto
Mariano
M
Cansado
José
J
D006706:Homeostasis / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D020239:Receptor Cross-Talk / Q000187:drug effects; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013312:Stress, Physiological / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism
D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D029702:Schizosaccharomyces pombe Proteins; C000617313:cpc2 protein, S pombe; D014443:Tyrosine; D006861:Hydrogen Peroxide