Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression

Marión, Rosa M.; Regev, Aviv; Segal, Eran; Barash, Yoseph; Koller, Daphne; Friedman, Nir; O’Shea, Erin K.

doi:10.1073/pnas.0405353101

Cited by 362 publications

(418 citation statements)

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“…It was reported that PKA promotes nuclear localization and binding of the transcriptional activator Sfp1 to the promoters of ribosomal protein genes (Marion et al 2004). In addition, PKA appears to induce transcription of ribosomal protein genes also by inhibition of Yak1, which in turn is required to promote the activity of the transcriptional corepressor Crf1 ).…”

Section: Regulation Of the Camp-pka Pathwaymentioning

confidence: 99%

“…TORC1 regulates, probably via direct phosphorylation, the nucleocytoplasmic distribution and the promoter binding of Sfp1. In exponentially growing cells, Sfp1 is localized in the nucleus where it promotes both RP as well as Ribi gene expression, but upon TORC1 inactivation Sfp1 translocates to the cytoplasm (Jorgensen et al 2004;Marion et al 2004;Lempiainen et al 2009). Sfp1, in turn, appears to affect the localization of the Fhl1-Ifh1 complex.…”

Section: Rapamycin-sensitive Signalling Via Torc1mentioning

confidence: 99%

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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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Section: Regulation Of the Camp-pka Pathwaymentioning

confidence: 99%

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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“…The TOR-RAS-PKA branch also regulates the localization of the stress-responsive transcription factor Sfp1, which activates the RP and ribosome biogenesis regulons to promote ribosome synthesis in parallel to Sch9. Sfp1 is mainly nuclear under normal growth conditions but dislodges nuclear FHL1 and IFH1 under different stress treatments to repress cell growth (Jorgensen et al, 2004;Marion et al, 2004). Whether a similar mechanism operates in mammals is not known.…”

Section: Introductionmentioning

confidence: 99%

Stress and mTORture signaling

2006

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“…The forkhead-like protein Fhl1 and an interacting factor Ifh1 constitute one axis of RP gene regulation Schawalder et al, 2004;Wade et al, 2004;Rudra et al, 2005). A second regulator that localizes to RP gene promoters is the split Zn-finger transcription factor Sfp1 (Fingerman et al, 2003;Jorgensen et al, 2004;Marion et al, 2004). RP gene expression is regulated by PKA through both Fhl1 and Sfp1 (Jorgensen et al, 2004).…”

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confidence: 99%

Arsenic Toxicity to Saccharomyces cerevisiae Is a Consequence of Inhibition of the TORC1 Kinase Combined with a Chronic Stress Response

Hosiner

Lempiäinen

Reiter³

et al. 2009

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The conserved Target Of Rapamycin (TOR) growth control signaling pathway is a major regulator of genes required for protein synthesis. The ubiquitous toxic metalloid arsenic, as well as mercury and nickel, are shown here to efficiently inhibit the rapamycin-sensitive TORC1 (TOR complex 1) protein kinase. This rapid inhibition of the TORC1 kinase is demonstrated in vivo by the dephosphorylation and inactivation of its downstream effector, the yeast S6 kinase homolog Sch9. Arsenic, mercury, and nickel cause reduction of transcription of ribosome biogenesis genes, which are under the control of Sfp1, a TORC1-regulated transcriptional activator. We report that arsenic stress deactivates Sfp1 as it becomes dephosphorylated, dissociates from chromatin, and exits the nucleus. Curiously, whereas loss of SFP1 function leads to increased arsenic resistance, absence of TOR1 or SCH9 has the opposite effect suggesting that TORC1 has a role beyond down-regulation of Sfp1. Indeed, we show that arsenic activates the transcription factors Msn2 and Msn4 both of which are targets of TORC1 and protein kinase A (PKA). In contrast to TORC1, PKA activity is not repressed during acute arsenic stress. A normal level of PKA activity might serve to dampen the stress response since hyperactive Msn2 will decrease arsenic tolerance. Thus arsenic toxicity in yeast might be determined by the balance between chronic activation of general stress factors in combination with lowered TORC1 kinase activity. INTRODUCTIONThe transition metal arsenic has a long history of human exploitation as both a poison and a medicine. In more recent times EhrlichЈs discovery of the antisyphilitic drug arsphenamine (also known as salvarsan) by systematic chemical modification of arsenic derivatives marked the beginning of modern pharmaceutical research. Arsenic trioxide (ATO) is used today in cancer treatment (Evens et al., 2004;Lu et al., 2007;Wang and Chen, 2008).Exposure to arsenic evokes a broad spectrum of cellular reactions in Saccharomyces cerevisiae Haugen et al., 2004;Jin, 2008;Thorsen et al., 2007) and in higher eukaryotes (Salnikow and Zhitkovich, 2008). A number of mechanisms exist for detoxification, probably because arsenic has always been widespread in the environment. These involve reduction of influx through the aquaglyceroporin Fps1p Thorsen et al., 2006); sequestration into the vacuole in the form of glutathione conjugates, metallothionein, and other metal/protein complexes; and active extrusion (Ghosh et al., 1999). In yeast, genome-wide analysis of the transcription patterns in response to arsenic revealed a complex network of transcription factors controlling the expression of several hundred genes (Haugen et al., 2004;Wysocki et al., 2004;Thorsen et al., 2007). Mitogen-activated protein kinases mediate protective responses involving AP-1-and AP-1-like transcription factors in higher eukaryotes and in fungi (Cavigelli et al., 1996;Rodriguez-Gabriel and Russell, 2005;Thorsen et al., 2006).The mechanisms by which arsenic might influence signalin...

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Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression

Cited by 362 publications

References 51 publications

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

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

Stress and mTORture signaling

Arsenic Toxicity to Saccharomyces cerevisiae Is a Consequence of Inhibition of the TORC1 Kinase Combined with a Chronic Stress Response

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