title: Ubp8 and SAGA regulate Snf1 AMP kinase activity.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Center forCancer Epigenetics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 1000, Houston, Texas 77030, USA.
authors.forename: Marenda A
authors.initials: MA
authors.lastname: Wilson
authors.forename: Evangelia
authors.initials: E
authors.lastname: Koutelou
authors.forename: Calley
authors.initials: C
authors.lastname: Hirsch
authors.forename: Kadir
authors.initials: K
authors.lastname: Akdemir
authors.forename: Andria
authors.initials: A
authors.lastname: Schibler
authors.forename: Michelle Craig
authors.initials: MC
authors.lastname: Barton
authors.forename: Sharon Y R
authors.initials: SY
authors.lastname: Dent
mesh_terms: D055372:AMP-Activated Protein Kinases; D000107:Acetylation; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D040901:Proteomics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D054875:Ubiquitination; D000099224:p300-CBP-Associated Factor
chemical_list: D055372:AMP-Activated Protein Kinases; D010450:Endopeptidases; D051548:Histone Acetyltransferases; D006657:Histones; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; C507785:SAGA complex, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor; C071570:SNF1-related protein kinases; C503322:UBP8 protein, S cerevisiae