Combinatorial Repression of the Hypoxic Genes of
            <i>Saccharomyces cerevisiae</i>
            by DNA Binding Proteins Rox1 and Mot3

Klinkenberg, Lee G.; Mennella, Thomas A.; Luetkenhaus, Katharina; Zitomer, R S

doi:10.1128/ec.4.4.649-660.2005

Cited by 54 publications

(71 citation statements)

References 50 publications

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“…Tup1p corepressor is required for transcriptional repression of PAU by oxygen. In contrast, Rox1p, a DNA-binding repressor involved in oxygen-dependent repression of other target genes such as ANB1, is not required (36). TUP1 and CYC8, two subunits of Tup1p-Cyc8p corepressor complex, were slightly down-regulated in our microarray experiment (70% at the 11th generation relative to the 1st generation).…”

Section: Discussionmentioning

confidence: 76%

Changes in Transcription and Metabolism During the Early Stage of Replicative Cellular Senescence in Budding Yeast

Kamei

Tamada

Nakayama

et al. 2014

Journal of Biological Chemistry

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Background: Senescence is the biological process of age-related cellular and organismal deterioration in function. Results: The transcriptome and metabolome at early stages of replicative senescence of yeast cells were measured. Conclusion: The transcriptomic and metabolomic profiles drastically changed at about half of the average replicative lifespan. Significance: This is the first integrated information on transcriptome and metabolome of aging yeast cells.

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Section: Discussionmentioning

confidence: 76%

Changes in Transcription and Metabolism During the Early Stage of Replicative Cellular Senescence in Budding Yeast

Kamei

Tamada

Nakayama

et al. 2014

Journal of Biological Chemistry

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“…In addition, the Rim101 pathway and Mot3 are linked via the Tup1-Cyc8 repression complex. Gene repression by Rim101 was shown to be dependent on Tup1-Cyc8 (Park et al, 1999;Lamb and Mitchell, 2003;Rothfels et al, 2005), and Mot3 is reportedly involved in the recruitment of Tup1-Cyc8 to its target sites (Klinkenberg et al, 2005). Therefore, the possibility cannot be excluded that links exist among the Rim101 pathway, Mck1, and Mot3.…”

Section: Discussionmentioning

confidence: 89%

The Rim101 Pathway Is Involved in Rsb1 Expression Induced by Altered Lipid Asymmetry

Ikeda

Kihara

Denpoh

et al. 2008

MBoC

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Biological membranes consist of lipid bilayers. The lipid compositions between the two leaflets of the plasma membrane differ, generating lipid asymmetry. Maintenance of proper lipid asymmetry is physiologically quite important, and its collapse induces several cellular responses including apoptosis and platelet coagulation. Thus, a change in lipid asymmetry must be restored to maintain "lipid asymmetry homeostasis." However, to date no lipid asymmetry-sensing proteins or any related downstream signaling pathways have been identified. We recently demonstrated that expression of the putative yeast sphingoid long-chain base transporter/translocase Rsb1 is induced when glycerophospholipid asymmetry is altered. Using mutant screening, we determined that the pH-responsive Rim101 pathway, the protein kinase Mck1, and the transcription factor Mot3 all act in lipid asymmetry signaling, and that the Rim101 pathway was activated in response to a change in lipid asymmetry. The activated transcription factor Rim101 induces Rsb1 expression via repression of another transcription repressor, Nrg1. Changes in lipid asymmetry are accompanied by cell surface exposure of negatively charged phospholipids; we speculate that the Rim101 pathway recognizes the surface charges. INTRODUCTIONBiological membranes are composed of lipid bilayers, and in the plasma membrane the lipid compositions differ between the two leaflets, resulting in asymmetry. Glycerophospholipids and sphingolipids contribute greatly to such asymmetry. Phosphatidylcholine (PC) and complex sphingolipids, including sphingomyelin (SM) and glycosphingolipids in mammals and myo-inositol-containing sphingolipids in the yeast Saccharomyces cerevisiae, are located mainly in the outer (extracytosolic) leaflet. Conversely, phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) are confined to the inner (cytosolic) leaflet (Pomorski et al., 2004;Ikeda et al., 2006). The hydrophilic nature of the headgroups of these amphiphilic lipids hinders their ability to traverse the hydrophobic membrane interior, and spontaneous flip-flop of the protein-free model membrane occurs only in low frequency (Bai and Pagano, 1997). However, situated in the biological membranes are enzymes called lipid translocases or flippases, which catalyze the transbilayer movement of lipids and establish their asymmetry. Recent studies have identified three classes of translocases/transporters for glycerophospholipids: ABC transporters, P-type ATPases, and scramblases (Holthuis and Levine, 2005;Ikeda et al., 2006). ABC transporters catalyze flop, which is the movement from the cytosolic to extracytosolic leaflet, whereas P-type ATPases stimulate flip, the reverse movement. Scramblases randomize the lipid distribution between the two leaflets. Sometimes, discriminating between a translocase and transporter is difficult. For example, it is unclear whether a lipid in one leaflet is directly translocated to the other leaflet or is first transported to the other side of the hydrophil...

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“…Mot3p modulates the transcription of a diverse set of genes in a dosage-dependent manner (Grishin et al 1998;Abramova et al 2001a). Mot3p acts in combination with Rox1p to recruit the Tup1-Ssn6 repressor complex to anaerobically expressed genes under aerobic conditions (Kastaniotis and Zitomer 2000;Mennella et al 2003;Sertil et al 2003;Klinkenberg et al 2005). Mot3p inhibited Ecm22p, but not Upc2p (Figure 3), and the direct physical interaction of Mot3p with Ecm22p ( Figure 5) was likely an important part of the inhibitory mechanism.…”

Section: Discussionmentioning

confidence: 99%

A Role for Sterol Levels in Oxygen Sensing in Saccharomyces cerevisiae

Davies¹,

2006

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Upc2p and Ecm22p are a pair of transcription factors responsible for the basal and induced expression of genes encoding enzymes of ergosterol biosynthesis in yeast (ERG genes). Upc2p plays a second role as a regulator of hypoxically expressed genes. Both sterols and heme depend upon molecular oxygen for their synthesis, and thus the levels of both have the potential to act as indicators of the oxygen environment of cells. Hap1p is a heme-dependent transcription factor that both Upc2 and Ecm22p depend upon for basal level expression of ERG genes. However, induction of both ERG genes and the hypoxically expressed DAN/ TIR genes by Upc2p and Ecm22p occurred in response to sterol depletion rather than to heme depletion. Indeed, upon sterol depletion, Upc2p no longer required Hap1p to activate ERG genes. Mot3p, a broadly acting repressor/activator protein, was previously shown to repress ERG gene expression, but the mechanism was unclear. We established that Mot3p bound directly to Ecm22p and repressed Ecm22p-but not Upc2p-mediated gene induction.

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Combinatorial Repression of the Hypoxic Genes of Saccharomyces cerevisiae by DNA Binding Proteins Rox1 and Mot3

Abstract: Integrating these results, we were able to devise a set of rules that govern the combinatorial interactions between Rox1 and Mot3 to achieve differential repression.

Cited by 54 publications

References 50 publications

Changes in Transcription and Metabolism During the Early Stage of Replicative Cellular Senescence in Budding Yeast

Changes in Transcription and Metabolism During the Early Stage of Replicative Cellular Senescence in Budding Yeast

The Rim101 Pathway Is Involved in Rsb1 Expression Induced by Altered Lipid Asymmetry

A Role for Sterol Levels in Oxygen Sensing in Saccharomyces cerevisiae

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