Elm1p Is One of Three Upstream Kinases for the Saccharomyces cerevisiae SNF1 Complex

Sutherland, Catherine M.; Hawley, Simon A.; McCartney, Rhonda R.; Leech, Anna; Stark, Michael J. R.; Schmidt, Martin C.; Hardie, D. Grahame

doi:10.1016/s0960-9822(03)00459-7

Cited by 245 publications

(235 citation statements)

References 31 publications

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“…One of the most studied modes of Snf1 regulation is the phosphorylation of threonine 210, a mark which closely follows Snf1 activation (14,24,36). In this study, we found that in addition to being modified by phosphorylation, Snf1 is modified by ubiquitination.…”

Section: Discussionmentioning

confidence: 51%

“…Here, we report that Ubp8 can deubiquitinate Snf1, a highly conserved AMP-activated serine/threonine protein kinase that serves as an energy sensor in the cell. Our data indicate that hyperubiquitination of Snf1 affects its stability as well as its phosphorylation status, which is known to affect Snf1 kinase activity (14,24,36). Together, our results suggest that SAGA functions as a master regulator of gene expression not only by altering chromatin structures but also by regulating the stability and activity of transcriptional modulators.…”

mentioning

confidence: 57%

“…One highly conserved mechanism involves the phosphorylation of the T loop at threonine 210 (T210) (14,19,24,36), which closely parallels the activation of Snf1 and many other AMP kinases. When yeast cells grown in glucose are switched to less-preferred carbon sources, Snf1 becomes phosphorylated and then activates the expression of genes involved in utilization of these carbon sources by regulating the activity of downstream transcriptional modulators (12,20,28,29,33,39).…”

Section: Resultsmentioning

confidence: 99%

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Ubp8 and SAGA Regulate Snf1 AMP Kinase Activity

Wilson

Koutelou

Hirsch

et al. 2011

Molecular and Cellular Biology

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Posttranslational modifications of histone proteins play important roles in the modulation of gene expression. The Saccharomyces cerevisiae (yeast) 2-MDa SAGA (Spt-Ada-Gcn5) complex, a well-studied multisubunit histone modifier, regulates gene expression through Gcn5-mediated histone acetylation and Ubp8-mediated histone deubiquitination. Using a proteomics approach, we determined that the SAGA complex also deubiquitinates nonhistone proteins, including Snf1, an AMP-activated kinase. Ubp8-mediated deubiquitination of Snf1 affects the stability and phosphorylation state of Snf1, thereby affecting Snf1 kinase activity. Others have reported that Gal83 is phosphorylated by Snf1, and we found that deletion of UBP8 causes decreased phosphorylation of Gal83, which is consistent with the effects of Ubp8 loss on Snf1 kinase functions. Overall, our data indicate that SAGA modulates the posttranslational modifications of Snf1 in order to fine-tune gene expression levels.Ubiquitination of cellular targets regulates many biological processes, from intracellular trafficking to gene expression. Although ubiquitination by ubiquitin (Ub) ligases is widely studied, less is known about subsequent deubiquitination (DUB) of cellular substrates. The identification of genes coding 16 deubiquitinases in the Saccharomyces cerevisiae (yeast) genome and genes coding at least 60 deubiquitinases in the human genome suggests that not only is deubiquitination important but also that deubiquitination may also occur in a substratespecific manner to regulate specific cellular processes. Despite the lack of knowledge of the targets of many of these deubiquitinases, it is known that some of these enzymes impact cellular growth and function (3,21,46). Overexpression of certain deubiquitinases is associated with progression of malignancy in neuroblastomas and a variety of carcinomas, indicating that these enzymes may be oncogenic (27,31,38).USP22, a deubiquitinase associated with the SAGA histone acetyltransferase (HAT) complex, was identified as a member of an 11-gene "death-from-cancer" signature that serves as a predictor of treatment resistance, aggressive growth, and metastasis of human tumors when overexpressed (7,8). The SAGA complex is highly conserved, and its functions are best characterized in yeast (4,9,17,23,35). In addition to acetylating histone H3 via the Gcn5 subunit, SAGA also proteolytically cleaves ubiquitin moieties from histone H2B via the Ubp8 subunit, which is an ortholog of USP22 (13, 47). Ubp8-mediated deubiquitination of histone H2B regulates the expression of target genes by modulating the level of histone H3 lysine 4 methylation, a mark that is associated with active transcription (13). In addition, Ubp8 facilitates the recruitment of the Cterminal domain kinase (Ctk1) to target gene promoters via histone H2B deubiquitination, which facilitates the transition from transcription initiation to elongation (43).Interestingly, recent studies indicate that the functions of USP22 extend beyond histone H2B, as it also deubiquiti...

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Section: Discussionmentioning

confidence: 51%

mentioning

confidence: 57%

Section: Resultsmentioning

confidence: 99%

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Ubp8 and SAGA Regulate Snf1 AMP Kinase Activity

Wilson

Koutelou

Hirsch

et al. 2011

Molecular and Cellular Biology

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“…Three upstream kinases, Sak1, Elm1 and Tos3, are responsible for phosphorylation of this threonine residue (Sutherland et al 2003). These kinases appear to be functionally redundant, since only the absence of all three causes a snf1D mutant phenotype.…”

Section: Structure and Regulation Of The Snf1 Kinasementioning

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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“…The SNF1 active protein kinase complex also includes the activating gamma subunit Snf4p (Celenza and Carlson, 1989), and one of three alternate regulatory beta subunits (Sip1p, Sip2p, and Gal83p; Yang et al, 1992Yang et al, , 1994Erickson and Johnston, 1993). Like other protein kinases, SNF1 activity is regulated by upstream kinases, Sak1p (Pak1p), Elm1p and Tos3p (Hong et al, 2003;Sutherland et al, 2003), and protein phosphatases, Reg1p-Glc7p (Sanz et al, 2000). Other levels of regulation include autoinhibition (Leech et al, 2003) and control of its subcellular localization (Hedbacker et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Isolation and characterization of the carbon catabolite‐derepressing protein kinase Snf1 from the stress tolerant yeast Torulaspora delbrueckii

Hernandez-Lopez

Prieto

Rández-Gil

2010

Yeast

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We cloned a genomic DNA fragment of the yeast Torulaspora delbrueckii by complementation of a Saccharomyces cerevisiae snf1 mutant strain. DNA sequence analysis revealed that the fragment contained a complete open reading frame (ORF), which shares a high similarity with the S. cerevisiae energy sensor protein kinase Snf1. The cloned TdSNF1 gene was able to restore growth of the S. cerevisiae snf1 mutant strain on media containing nonfermentable carbon sources. Furthermore, cells of the Tdsnf1 mutant were unable to proliferate under nonfermenting conditions. Finally, protein domain analysis showed that TdSnf1p contains a typical catalytic protein kinase domain (positions 41-293), which is also present in other Snf1p homologues. Within this region we identified a protein kinase ATP-binding region (positions 48-71) and a consensus Ser/Thr protein kinase active site (positions 160-172). The GenBank Accession No. for the sequenced DNA fragment is HM131845.

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Elm1p Is One of Three Upstream Kinases for the Saccharomyces cerevisiae SNF1 Complex

Abstract: Elm1p, Pak1p, and Tos3p are upstream kinases for the SNF1 complex that have partially redundant functions.

Cited by 245 publications

References 31 publications

Ubp8 and SAGA Regulate Snf1 AMP Kinase Activity

Ubp8 and SAGA Regulate Snf1 AMP Kinase Activity

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

Isolation and characterization of the carbon catabolite‐derepressing protein kinase Snf1 from the stress tolerant yeast Torulaspora delbrueckii

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