The role of the RACK1 ortholog Cpc2p in modulating pheromone-induced cell cycle arrest in fission yeast

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Abstract

The detection and amplification of extracellular signals requires the involvement of multiple protein components. In mammalian cells the receptor of activated C kinase (RACK1) is an important scaffolding protein for signal transduction networks. Further, it also performs a critical function in regulating the cell cycle by modulating the G1/S transition. Many eukaryotic cells express RACK1 orthologs, with one example being Cpc2p in the fission yeast Schizosaccharomyces pombe. In contrast to RACK1, Cpc2p has been described to positively regulate, at the ribosomal level, cells entry into M phase. In addition, Cpc2p controls the stress response pathways through an interaction with Msa2p, and sexual development by modulating Ran1p/Pat1p. Here we describe investigations into the role, which Cpc2p performs in controlling the G protein-mediated mating response pathway. Despite structural similarity to Gβ-like subunits, Cpc2p appears not to function at the G protein level. However, upon pheromone stimulation, cells overexpressing Cpc2p display substantial cell morphology defects, disorientation of septum formation and a significantly protracted G1 arrest. Cpc2p has the potential to function at multiple positions within the pheromone response pathway. We provide a mechanistic interpretation of this novel data by linking Cpc2p function, during the mating response, with its previous described interactions with Ran1p/Pat1p. We suggest that overexpressing Cpc2p prolongs the stimulated state of pheromone-induced cells by increasing ste11 gene expression. These data indicate that Cpc2p regulates the pheromone-induced cell cycle arrest in fission yeast by delaying cells entry into S phase.

Item Type: Journal Article
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QR Microbiology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Cytology, Cell receptors, Cytology -- Research, Eukaryotic cells, Proteins -- Research
Journal or Publication Title: PLoS One
Publisher: Public Library of Science
ISSN: 1932-6203
Official Date: 3 July 2013
Dates:
Date
Event
3 July 2013
Published
Volume: Volume 8
Number: Number 7
Page Range: Article number e65927
DOI: 10.1371/journal.pone.0065927
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons open licence)
Date of first compliant deposit: 24 December 2015
Date of first compliant Open Access: 24 December 2015
Funder: Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC) , University Hospitals Coventry and Warwickshire NHS Trust, Science City Research Alliance, Consejo Nacional de Ciencia y Tecnología (Mexico) [Mexican Council for Science and Technology] (CONACYT)
Grant number: BB/G01227X/1 (BBSRC)
URI: https://wrap.warwick.ac.uk/55445/

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