Sfp1 Plays a Key Role in Yeast Ribosome Biogenesis

Fingerman, Ian M.; Nagaraj, Vijayalakshmi H.; Norris, David; Vershon, Andrew K.

doi:10.1128/ec.2.5.1061-1068.2003

Cited by 110 publications

(143 citation statements)

References 29 publications

(49 reference statements)

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“…In addition to Ras/protein kinase A and TOR, Sfp1 and Sch9 are likely involved in coordinating the expression of these two networks, given their role in dictating critical cell size at the G 1 /S transition and coordinating the expression of genes for ribosomal biogenesis (22,43,59). Although few of the genes encoding structural components of the ribosomes were significantly (P Ͻ 0.01) affected here, many (ϳ80) do show a kinetically similar trend of down-regulation but with lower confidence (P Ͼ 0.01).…”

Section: Discussionmentioning

confidence: 99%

“…Such a transcriptional program makes functional sense given the acute interruption in the steady-state rate of energy production during the switch from mixed respirofermentative to strictly fermentative growth in galactose. Although no factors have been identified that directly bind to PAC or RRPE, Sfp1, and/or Sch9 are likely involved given their role in regulating nucleolar genes for ribosomal biogenesis and translation at START (22,43,59).…”

Section: Figmentioning

confidence: 99%

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Dynamical Remodeling of the Transcriptome during Short-Term Anaerobiosis in Saccharomyces cerevisiae: Differential Response and Role of Msn2 and/or Msn4 and Other Factors in Galactose and Glucose Media

Lai¹,

Kosorukoff

Burke³

et al. 2005

Molecular and Cellular Biology

117

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In contrast to previous steady-state analyses of the O 2 -responsive transcriptome, here we examined the dynamics of the response to short-term anaerobiosis (2 generations) in both catabolite-repressed (glucose) and derepressed (galactose) cells, assessed the specific role that Msn2 and Msn4 play in mediating the response, and identified gene networks using a novel clustering approach. Upon shifting cells to anaerobic conditions in galactose medium, there was an acute (ϳ10 min) yet transient (<45 min) induction of Msn2-and/or Msn4-regulated genes associated with the remodeling of reserve energy and catabolic pathways during the switch from mixed respiro-fermentative to strictly fermentative growth. Concomitantly, MCB-and SCB-regulated networks associated with the G 1 /S transition of the cell cycle were transiently down-regulated along with rRNA processing genes containing PAC and RRPE motifs. Remarkably, none of these gene networks were differentially expressed when cells were shifted in glucose, suggesting that a metabolically derived signal arising from the abrupt cessation of respiration, rather than O 2 deprivation per se, elicits this "stress response." By ϳ0.2 generation of anaerobiosis in both media, more chronic, heme-dependent effects were observed, including the down-regulation of Hap1-regulated networks, derepression of Rox1-regulated networks, and activation of Upc2-regulated ones. Changes in these networks result in the functional remodeling of the cell wall, sterol and sphingolipid metabolism, and dissimilatory pathways required for long-term anaerobiosis. Overall, this study reveals that the acute withdrawal of oxygen can invoke a metabolic state-dependent "stress response" but that acclimatization to oxygen deprivation is a relatively slow process involving complex changes primarily in heme-regulated gene networks.

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Section: Discussionmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

Dynamical Remodeling of the Transcriptome during Short-Term Anaerobiosis in Saccharomyces cerevisiae: Differential Response and Role of Msn2 and/or Msn4 and Other Factors in Galactose and Glucose Media

Lai¹,

Kosorukoff

Burke³

et al. 2005

Molecular and Cellular Biology

117

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“…Regulation of expression of the ribosome biogenesis regulon (RiBi) and the ribosomal proteins themselves has recently been elucidated in yeast (Jorgensen et al, 2002) with the discovery of two transcription factors, Sfp1 and Sch9, which function in the Ras/PKA and TOR signaling pathways to control the ribosome biosynthetic rate (Fingerman et al, 2003;Jorgensen et al, 2004a;Marion et al, 2004). It has been proposed that expression of the RiBi regulon also affects the cell size setpoint for Start, because mutations that inhibit RiBi expression result in small cells passing Start (Jorgensen et al, 2002;Jorgensen and Tyers, 2004).…”

Section: Introductionmentioning

confidence: 99%

Ribosome Biogenesis Is Sensed at the Start Cell Cycle Checkpoint

Bernstein

Bleichert

Bean

et al. 2007

MBoC

120

122

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In the yeast Saccharomyces cerevisiae it has long been thought that cells must reach a critical cell size, called the “setpoint,” in order to allow the Start cell cycle transition. Recent evidence suggests that this setpoint is lowered when ribosome biogenesis is slowed. Here we present evidence that yeast can sense ribosome biogenesis independently of mature ribosome levels and protein synthetic capacity. Our results suggest that ribosome biogenesis directly promotes passage through Start through Whi5, the yeast functional equivalent to the human tumor suppressor Rb. When ribosome biogenesis is inhibited, a Whi5-dependent mechanism inhibits passage through Start before significant decreases in both the number of ribosomes and in overall translation capacity of the cell become evident. This delay at Start in response to decreases in ribosome biogenesis occurs independently of Cln3, the major known Whi5 antagonist. Thus ribosome biogenesis may be sensed at multiple steps in Start regulation. Ribosome biogenesis may thus both delay Start by increasing the cell size setpoint and independently may promote Start by inactivating Whi5.

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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).…”

Section: Introductionmentioning

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

MBoC

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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 Plays a Key Role in Yeast Ribosome Biogenesis

Cited by 110 publications

References 29 publications

Dynamical Remodeling of the Transcriptome during Short-Term Anaerobiosis in Saccharomyces cerevisiae: Differential Response and Role of Msn2 and/or Msn4 and Other Factors in Galactose and Glucose Media

Dynamical Remodeling of the Transcriptome during Short-Term Anaerobiosis in Saccharomyces cerevisiae: Differential Response and Role of Msn2 and/or Msn4 and Other Factors in Galactose and Glucose Media

Ribosome Biogenesis Is Sensed at the Start Cell Cycle Checkpoint

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

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