Ubp8 and SAGA Regulate Snf1 AMP Kinase Activity

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2011 Jun 2

PMID 21628526

Citations 26

Authors

Marenda A Wilson

Evangelia Koutelou

Calley Hirsch

Kadir Akdemir

Andria Schibler

Michelle Craig Barton

Sharon Y R Dent

Affiliations

Soon will be listed here.

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.

Citing Articles

Glucose Inhibits Yeast AMPK (Snf1) by Three Independent Mechanisms.

Simpson-Lavy K, Kupiec M Biology (Basel). 2023; 12(7).

PMID: 37508436 PMC: 10376661. DOI: 10.3390/biology12071007.

Posttranslational regulation of the GCN5 and PCAF acetyltransferases.

Ononye O, Downey M PLoS Genet. 2022; 18(9):e1010352.

PMID: 36107838 PMC: 9477270. DOI: 10.1371/journal.pgen.1010352.

Deubiquitination in prostate cancer progression: role of USP22.

Nag N, Dutta S J Cancer Metastasis Treat. 2021; 6.

PMID: 34660907 PMC: 8516349. DOI: 10.20517/2394-4722.2020.23.

Kog1/Raptor mediates metabolic rewiring during nutrient limitation by controlling SNF1/AMPK activity.

Rashida Z, Srinivasan R, Cyanam M, Laxman S Sci Adv. 2021; 7(16).

PMID: 33853774 PMC: 8046376. DOI: 10.1126/sciadv.abe5544.

Post-Translational Modifications of the Energy Guardian AMP-Activated Protein Kinase.

Ovens A, Scott J, Langendorf C, Kemp B, Oakhill J, Smiles W Int J Mol Sci. 2021; 22(3).

PMID: 33513781 PMC: 7866021. DOI: 10.3390/ijms22031229.

References

Yuan J, Luo K, Zhang L, Cheville J, Lou Z . USP10 regulates p53 localization and stability by deubiquitinating p53. Cell. 2010; 140(3):384-96. PMC: 2820153. DOI: 10.1016/j.cell.2009.12.032. View

Hedges D, Proft M, Entian K . CAT8, a new zinc cluster-encoding gene necessary for derepression of gluconeogenic enzymes in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1995; 15(4):1915-22. PMC: 230417. DOI: 10.1128/MCB.15.4.1915. View

Steinberg G, Kemp B . AMPK in Health and Disease. Physiol Rev. 2009; 89(3):1025-78. DOI: 10.1152/physrev.00011.2008. View

Ingvarsdottir K, Krogan N, Emre N, Wyce A, Thompson N, Emili A . H2B ubiquitin protease Ubp8 and Sgf11 constitute a discrete functional module within the Saccharomyces cerevisiae SAGA complex. Mol Cell Biol. 2005; 25(3):1162-72. PMC: 544016. DOI: 10.1128/MCB.25.3.1162-1172.2005. View

Pereg Y, Liu B, ORourke K, Sagolla M, Dey A, Komuves L . Ubiquitin hydrolase Dub3 promotes oncogenic transformation by stabilizing Cdc25A. Nat Cell Biol. 2010; 12(4):400-6. DOI: 10.1038/ncb2041. View

Daniel T, Carling D . Expression and regulation of the AMP-activated protein kinase-SNF1 (sucrose non-fermenting 1) kinase complexes in yeast and mammalian cells: studies using chimaeric catalytic subunits. Biochem J. 2002; 365(Pt 3):629-38. PMC: 1222717. DOI: 10.1042/BJ20020124. View

Hong S, Leiper F, Woods A, Carling D, Carlson M . Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases. Proc Natl Acad Sci U S A. 2003; 100(15):8839-43. PMC: 166400. DOI: 10.1073/pnas.1533136100. View

Yaglom J, Linskens M, Sadis S, Rubin D, Futcher B, Finley D . p34Cdc28-mediated control of Cln3 cyclin degradation. Mol Cell Biol. 1995; 15(2):731-41. PMC: 231941. DOI: 10.1128/MCB.15.2.731. View

Martinez E . Multi-protein complexes in eukaryotic gene transcription. Plant Mol Biol. 2003; 50(6):925-47. DOI: 10.1023/a:1021258713850. View

10.

Grant P, Sterner D, Duggan L, Workman J, Berger S . The SAGA unfolds: convergence of transcription regulators in chromatin-modifying complexes. Trends Cell Biol. 1998; 8(5):193-7. DOI: 10.1016/s0962-8924(98)01263-x. View

11.

Smith F, DAVIES S, Wilson W, Carling D, Hardie D . The SNF1 kinase complex from Saccharomyces cerevisiae phosphorylates the transcriptional repressor protein Mig1p in vitro at four sites within or near regulatory domain 1. FEBS Lett. 1999; 453(1-2):219-23. DOI: 10.1016/s0014-5793(99)00725-5. View

12.

Hedbacker K, Carlson M . SNF1/AMPK pathways in yeast. Front Biosci. 2007; 13:2408-20. PMC: 2685184. DOI: 10.2741/2854. View

13.

Neurath K, Keough M, Mikkelsen T, Claffey K . AMP-dependent protein kinase alpha 2 isoform promotes hypoxia-induced VEGF expression in human glioblastoma. Glia. 2006; 53(7):733-43. DOI: 10.1002/glia.20326. View

14.

Daniel J, Grant P . Multi-tasking on chromatin with the SAGA coactivator complexes. Mutat Res. 2007; 618(1-2):135-48. PMC: 1892243. DOI: 10.1016/j.mrfmmm.2006.09.008. View

15.

Sanz P . Snf1 protein kinase: a key player in the response to cellular stress in yeast. Biochem Soc Trans. 2003; 31(Pt 1):178-81. DOI: 10.1042/bst0310178. View

16.

Vincent O, Townley R, Kuchin S, Carlson M . Subcellular localization of the Snf1 kinase is regulated by specific beta subunits and a novel glucose signaling mechanism. Genes Dev. 2001; 15(9):1104-14. PMC: 312685. DOI: 10.1101/gad.879301. View

17.

Machida Y, Machida Y, Vashisht A, Wohlschlegel J, Dutta A . The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1. J Biol Chem. 2009; 284(49):34179-88. PMC: 2797188. DOI: 10.1074/jbc.M109.046755. View

18.

Lee K, Florens L, Swanson S, Washburn M, Workman J . The deubiquitylation activity of Ubp8 is dependent upon Sgf11 and its association with the SAGA complex. Mol Cell Biol. 2005; 25(3):1173-82. PMC: 544014. DOI: 10.1128/MCB.25.3.1173-1182.2005. View

19.

Woods R, Gietz R . High-efficiency transformation of plasmid DNA into yeast. Methods Mol Biol. 2001; 177:85-97. DOI: 10.1385/1-59259-210-4:085. View

20.

Rahner A, Scholer A, Martens E, Gollwitzer B, Schuller H . Dual influence of the yeast Cat1p (Snf1p) protein kinase on carbon source-dependent transcriptional activation of gluconeogenic genes by the regulatory gene CAT8. Nucleic Acids Res. 1996; 24(12):2331-7. PMC: 145921. DOI: 10.1093/nar/24.12.2331. View