Hyperphosphorylation of Msn2p and Msn4p in response to heat shock and the diauxic shift is inhibited by cAMP in Saccharomyces cerevisiae

Garreau, Hervé; Hasan, Rukhsana; Renault, Georges; Estruch, Francisco; Boy‐Marcotte, Emmanuelle; Jacquet, Michel

doi:10.1099/00221287-146-9-2113

Cited by 129 publications

(125 citation statements)

References 31 publications

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“…To further test whether the observed slowdowns in nuclear translation, phosphorylation and protein mobility were specific to components of the HOG pathway, we examined the dynamics of the nuclear translocation of Msn2p (34)(35)(36), a key transcription factor in the general stress response of yeast. After hyperosmotic stress, Msn2p is hyperphosphorylated and imported into the nucleus (37).…”

Section: Resultsmentioning

confidence: 99%

Severe osmotic compression triggers a slowdown of intracellular signaling, which can be explained by molecular crowding

Miermont

Waharte

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

183

169

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Regulation of the cellular volume is fundamental for cell survival and function. Deviations from equilibrium trigger dedicated signaling and transcriptional responses that mediate water homeostasis and volume recovery. Cells are densely packed with proteins, and molecular crowding may play an important role in cellular processes. Indeed, increasing molecular crowding has been shown to modify the kinetics of biochemical reactions in vitro; however, the effects of molecular crowding in living cells are mostly unexplored. Here, we report that, in yeast, a sudden reduction in cellular volume, induced by severe osmotic stress, slows down the dynamics of several signaling cascades, including the stress-response pathways required for osmotic adaptation. We show that increasing osmotic compression decreases protein mobility and can eventually lead to a dramatic stalling of several unrelated signaling and cellular processes. The rate of these cellular processes decreased exponentially with protein density when approaching stalling osmotic compression. This suggests that, under compression, the cytoplasm behaves as a soft colloid undergoing a glass transition. Our results shed light on the physical mechanisms that force cells to cope with volume fluctuations to maintain an optimal protein density compatible with cellular functions.

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Section: Resultsmentioning

confidence: 99%

Severe osmotic compression triggers a slowdown of intracellular signaling, which can be explained by molecular crowding

Miermont

Waharte

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

183

169

View full text Add to dashboard Cite

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“…Upon glucose exhaustion, they are hyperphosphorylated and translocated to the nucleus, where they induce expression of the STREcontrolled genes. PKA inhibits nuclear import of Msn2/4, probably through direct phosphorylation of their nuclear localization signal (Gorner et al 1998(Gorner et al , 2002Garreau et al 2000). A second mechanism for PKA-mediated regulation of STRE-controlled gene expression involves the Ccr4-Not complex, a global transcriptional regulator that affects genes positively and negatively.…”

Section: Regulation Of the Camp-pka Pathwaymentioning

confidence: 99%

“…On the other hand, TORC1 inhibits the transcription of stress-responsive genes via a Rim15-independent, but Tap42-PP2A-dependent route, thereby promoting the phosphorylation and cytoplasmic retention of Msn2 (Beck and Hall 1999; Duvel et al 2003;Santhanam et al 2004). It is important to note that the latter is independent of the PKA-mediated phosphorylation of the Msn2/4 nuclear localization signal (Gorner et al 1998(Gorner et al , 2002Garreau et al 2000;Santhanam et al 2004).…”

Section: Rapamycin-sensitive Signalling Via Torc1mentioning

confidence: 99%

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

et al. 2010

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Cells of all living organisms contain complex signal transduction networks to ensure that a wide range of physiological properties are properly adapted to the environmental conditions. The fundamental concepts and individual building blocks of these signalling networks are generally well-conserved from yeast to man; yet, the central role that growth factors and hormones play in the regulation of signalling cascades in higher eukaryotes is executed by nutrients in yeast. Several nutrient-controlled pathways, which regulate cell growth and proliferation, metabolism and stress resistance, have been defined in yeast. These pathways are integrated into a signalling network, which ensures that yeast cells enter a quiescent, resting phase (G 0 ) to survive periods of nutrient scarceness and that they rapidly resume growth and cell proliferation when nutrient conditions become favourable again. A series of well-conserved nutrient-sensory protein kinases perform key roles in this signalling network: i.e. Snf1, PKA, Tor1 and Tor2, Sch9 and Pho85-Pho80. In this review, we provide a comprehensive overview on the current understanding of the signalling processes mediated via these kinases with a particular focus on how these individual pathways converge to signalling networks that ultimately ensure the dynamic translation of extracellular nutrient signals into appropriate physiological responses.

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“…Therefore, we examined whether yeast GSK-3 phosphorylates Msn2p in intact cells. It has been shown that heat shock and glucose starvation induce a mobility shift of Msn2p on an SDS gel, which reflects the phosphorylation of Msn2p (Garreau et al, 2000). After the wild-type strain and the gsk-3 null mutant had been subjected to salt stress, the yeast extracts were electrophoresed and probed with the anti-Myc antibody to detect Msn2p.…”

Section: Possible Mechanism Of Regulation Of Msn2p By Gsk-3mentioning

confidence: 99%

Yeast Glycogen Synthase Kinase-3 Activates Msn2p-dependent Transcription of Stress Responsive Genes

Hirata

Andoh²,

Asahara

et al. 2003

MBoC

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The yeast Saccharomyces cerevisiae has four genes, MCK1, MDS1 (RIM11), MRK1, and YOL128c, that encode homologues of mammalian glycogen synthase kinase 3 (GSK-3). A gsk-3 null mutant in which these four genes are disrupted showed growth defects on galactose medium. We isolated several multicopy suppressors of this growth defect. Two of them encoded Msn2p and phosphoglucomutase (PGM). Msn2p is a transcription factor that binds to the stress-response element (STRE). PGM is an enzyme that interconverts glucose-1 phosphate and glucose-6 phosphate and is regulated by Msn2p at the transcriptional level. Expression of the mRNAs of PGM2 and DDR2, whose promoter regions possess STRE sequences, on induction by heat shock or salt stress was reduced not only in an msn2 msn4 (msn2 homologue) double mutant but also in the gsk-3 null mutant. STRE-dependent transcription was greatly inhibited in the gsk-3 null mutant or mck1 mds1 double mutant, and this phenotype was suppressed by the expression of Mck1p but not of a kinase-inactive form of Mck1p. Although Msn2p accumulated in the nucleus of the gsk-3 null mutant as well as in the wild-type strain under various stress conditions, its STRE-binding activity was reduced in extracts prepared from the gsk-3 null mutant or mck1 mds1 double mutant. These results suggest that yeast GSK-3 promotes formation of a complex between Msn2p and DNA, which is required for the proper response to different forms of stress. Because neither Msn2p–GSK-3 complex formation nor GSK-3–dependent phosphorylation of Msn2p could be detected, the regulation of Msn2p by GSK-3 may be indirect

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Hyperphosphorylation of Msn2p and Msn4p in response to heat shock and the diauxic shift is inhibited by cAMP in Saccharomyces cerevisiae

Cited by 129 publications

References 31 publications

Severe osmotic compression triggers a slowdown of intracellular signaling, which can be explained by molecular crowding

Severe osmotic compression triggers a slowdown of intracellular signaling, which can be explained by molecular crowding

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

Yeast Glycogen Synthase Kinase-3 Activates Msn2p-dependent Transcription of Stress Responsive Genes

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