Mpt5p, a stress tolerance- and lifespan-promoting PUF protein in Saccharomyces cerevisiae, acts upstream of the cell wall integrity pathway

Stewart, M.S., Krause, S.A., McGhie, J. and Gray, J.V. (2007) Mpt5p, a stress tolerance- and lifespan-promoting PUF protein in Saccharomyces cerevisiae, acts upstream of the cell wall integrity pathway. Eukaryotic Cell, 6(2), pp. 262-270. (doi: 10.1128/EC.00188-06) (PMID:17172436) (PMCID:PMC1797943)

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Pumilio family (PUF) proteins affect specific genes by binding to, and inhibiting the translation or stability of, their transcripts. The PUF domain is required and sufficient for this function. One Saccharomyces cerevisiae PUF protein, Mpt5p (also called Puf5p or Uth4p), promotes stress tolerance and replicative life span (the maximum number of doublings a mother cell can undergo before entering into senescence) by an unknown mechanism thought to partly overlap with, but to be independent of, the cell wall integrity (CWI) pathway. Here, we found that mpt5{Delta} mutants also display a short chronological life span (the time cells stay alive in saturated cultures in synthetic medium), a defect that is suppressed by activation of CWI signaling. We found that Mpt5p is an upstream activator of the CWI pathway: mpt5{Delta} mutants display the appropriate phenotypes and genetic interactions, display low basal activity of the pathway, and are defective in activation of the pathway upon thermal stress. A set of mRNAs that specifically bind to Mpt5p was recently reported. One such putative target, LRG1, encodes a GTPase-activating protein for Rho1p that directly links Mpt5p to CWI signaling: Lrg1p inhibits CWI signaling, LRG1 mRNA contains a consensus Mpt5p-binding site in its putative 3' untranslated region, loss of Lrg1p suppresses the temperature sensitivity and CWI signaling defects of mpt5{Delta} mutants, and LRG1 mRNA abundance is inhibited by Mpt5p. We conclude that Mpt5p is required for normal replicative and chronological life spans and that the CWI pathway is a key and direct downstream target of this PUF protein.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Gray, Professor Joseph
Authors: Stewart, M.S., Krause, S.A., McGhie, J., and Gray, J.V.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Eukaryotic Cell
Publisher:American Society for Microbiology
ISSN (Online):1535-9786
Published Online:15 December 2006

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
352641A novel post-genomic approach to identify the functions of an essential protein - yeast protein kinase CJoseph GrayBiotechnology and Biological Sciences Research Council (BBSRC)C20144LS - BIOMOLECULAR SCIENCE