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PMID: 15282298 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The in vivo activity of Ime1, the key transcriptional activator of meiosis-specific genes in Saccharomyces cerevisiae, is inhibited by the cyclic AMP/protein kinase A signal pathway through the glycogen synthase kinase 3-beta homolog Rim11.

Molecular and cellular biology ·Vol. 24 ·No. 16 ·2004-08-00 ·Pages 6967-79

Rubin-Bejerano I, Sagee S, Friedman O, Pnueli L, Kassir Y

Abstract

Phosphorylation is the main mode by which signals are transmitted to key regulators of developmental pathways. The glycogen synthase kinase 3 family plays pivotal roles in the development and well-being of all eukaryotic organisms. Similarly, the budding yeast homolog Rim11 is essential for the exit of diploid cells from the cell cycle and for entry into the meiotic developmental pathway. In this report we show that in vivo, in cells grown in a medium promoting vegetative growth with acetate as the sole carbon source (SA medium), Rim11 phosphorylates Ime1, the master transcriptional activator required for entry into the meiotic cycle and for the transcription of early meiosis-specific genes. We demonstrate that in the presence of glucose, the kinase activity of Rim11 is inhibited. This inhibition could be due to phosphorylation on Ser-5, Ser-8, and/or Ser-12 because in the rim11S5AS8AS12A mutant, Ime1 is incorrectly phosphorylated in the presence of glucose and cells undergo sporulation. We further show that this nutrient signal is transmitted to Rim11 and consequently to Ime1 by the cyclic AMP/protein kinase A signal transduction pathway. Ime1 is phosphorylated in SA medium on at least two residues, Tyr-359 and Ser-302 and/or Ser-306. Ser-302 and Ser-306 are part of a consensus site for the mammalian homolog of Rim11, glycogen synthase kinase 3-beta. Phosphorylation on Tyr-359 but not Ser-302 or Ser-306 is essential for the transcription of early meiosis-specific genes and sporulation. We show that Tyr-359 is phosphorylated by Rim11.

MeSH Terms
Acetates/metabolism Culture Media/chemistry Cyclic AMP/metabolism Cyclic AMP-Dependent Protein Kinases/metabolism Gene Expression Regulation, Fungal Glucose/metabolism Glycogen Synthase Kinase 3/genetics,metabolism Glycogen Synthase Kinase 3 beta Intracellular Signaling Peptides and Proteins Meiosis/physiology Nitrogen/metabolism Nuclear Proteins/genetics,metabolism Phosphorylation Protein Processing, Post-Translational Protein Serine-Threonine Kinases/genetics,metabolism Saccharomyces cerevisiae/cytology,genetics,physiology Saccharomyces cerevisiae Proteins/genetics,metabolism Second Messenger Systems/physiology Serine/metabolism Transcription Factors/genetics,metabolism Transcription, Genetic Two-Hybrid System Techniques Tyrosine/metabolism
Chemicals
Acetates Culture Media IME1 protein, S cerevisiae Intracellular Signaling Peptides and Proteins Nuclear Proteins Saccharomyces cerevisiae Proteins Transcription Factors Tyrosine Serine Cyclic AMP Glycogen Synthase Kinase 3 beta Protein Serine-Threonine Kinases RIM11 protein, S cerevisiae Cyclic AMP-Dependent Protein Kinases Glycogen Synthase Kinase 3 Glucose Nitrogen
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Rubin-Bejerano Ifat
Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel. ykassir@techunix.technion.ac.il
Sagee Shira
Friedman Osnat
Pnueli Lilach
Kassir Yona
References (56)
56 references, click to expand
  1. A new efficient gene disruption cassette for repeated use in budding yeast.
    Nucleic Acids Res. 1996 Jul 1;24(13):2519-24 PMID: 8692690
  2. Induction of meiosis in Saccharomyces cerevisiae depends on conversion of the transcriptional represssor Ume6 to a positive regulator by its regulated association with the transcriptional activator Ime1.
    Mol Cell Biol. 1996 May;16(5):2518-26 PMID: 8628320
  3. Repression by Ume6 involves recruitment of a complex containing Sin3 corepressor and Rpd3 histone deacetylase to target promoters.
    Cell. 1997 May 2;89(3):365-71 PMID: 9150136
  4. Interaction of yeast repressor-activator protein Ume6p with glycogen synthase kinase 3 homolog Rim11p.
    Mol Cell Biol. 1997 Dec;17(12):7230-6 PMID: 9372955
  5. Multiple and distinct activation and repression sequences mediate the regulated transcription of IME1, a transcriptional activator of meiosis-specific genes in Saccharomyces cerevisiae.
    Mol Cell Biol. 1998 Apr;18(4):1985-95 PMID: 9528770
  6. The three yeast A kinases have specific signaling functions in pseudohyphal growth.
    Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13783-7 PMID: 9811878
  7. G1 cyclins block the Ime1 pathway to make mitosis and meiosis incompatible in budding yeast.
    EMBO J. 1999 Jan 15;18(2):320-9 PMID: 9889189
  8. Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae.
    Mol Cell Biol. 1999 Jul;19(7):4874-87 PMID: 10373537
  9. The yeast trimeric guanine nucleotide-binding protein alpha subunit, Gpa2p, controls the meiosis-specific kinase Ime2p activity in response to nutrients.
    Mol Cell Biol. 1999 Sep;19(9):6110-9 PMID: 10454558
  10. Phospholipase C binds to the receptor-like GPR1 protein and controls pseudohyphal differentiation in Saccharomyces cerevisiae.
    J Biol Chem. 1999 Oct 15;274(42):30052-8 PMID: 10514491
  11. The Ume6 regulon coordinates metabolic and meiotic gene expression in yeast.
    Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13431-6 PMID: 12370439
  12. Receptor-dependent and tyrosine phosphatase-mediated inhibition of GSK3 regulates cell fate choice.
    Dev Cell. 2002 Oct;3(4):523-32 PMID: 12408804
  13. Transcriptional regulation of meiosis in budding yeast.
    Int Rev Cytol. 2003;224:111-71 PMID: 12722950
  14. TOR regulates the subcellular localization of Ime1, a transcriptional activator of meiotic development in budding yeast.
    Mol Cell Biol. 2003 Oct;23(20):7415-24 PMID: 14517308
  15. Glucose and nitrogen regulate the switch from histone deacetylation to acetylation for expression of early meiosis-specific genes in budding yeast.
    Mol Cell Biol. 2004 Jun;24(12):5197-208 PMID: 15169885
  16. Initiation of meiosis in cell cycle initiation mutants of Saccharomyces cerevisiae.
    Exp Cell Res. 1978 Mar 15;112(2):241-8 PMID: 344051
  17. Initiation of meiosis in yeast mutants defective in adenylate cyclase and cyclic AMP-dependent protein kinase.
    Cell. 1983 Feb;32(2):417-23 PMID: 6297794
  18. Construction and use of gene fusions to lacZ (beta-galactosidase) that are expressed in yeast.
    Methods Enzymol. 1983;101:167-80 PMID: 6310320
  19. The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway.
    Cell. 1987 Mar 13;48(5):789-99 PMID: 3545497
  20. Cloning and characterization of BCY1, a locus encoding a regulatory subunit of the cyclic AMP-dependent protein kinase in Saccharomyces cerevisiae.
    Mol Cell Biol. 1987 Apr;7(4):1371-7 PMID: 3037314
  21. IME1, a positive regulator gene of meiosis in S. cerevisiae.
    Cell. 1988 Mar 25;52(6):853-62 PMID: 3280136
  22. Positive control of sporulation-specific genes by the IME1 and IME2 products in Saccharomyces cerevisiae.
    Mol Cell Biol. 1990 May;10(5):2104-10 PMID: 2183020
  23. Initiation of meiosis and sporulation in Saccharomyces cerevisiae requires a novel protein kinase homologue.
    Mol Gen Genet. 1990 Apr;221(2):176-86 PMID: 2196430
  24. The adenylate cyclase/protein kinase cascade regulates entry into meiosis in Saccharomyces cerevisiae through the gene IME1.
    EMBO J. 1990 Oct;9(10):3225-32 PMID: 2209544
  25. Getting started with yeast.
    Methods Enzymol. 1991;194:3-21 PMID: 2005794
  26. Monitoring meiosis and sporulation in Saccharomyces cerevisiae.
    Methods Enzymol. 1991;194:94-110 PMID: 2005827
  27. Efficient site-directed mutagenesis using uracil-containing DNA.
    Methods Enzymol. 1991;204:125-39 PMID: 1943776
  28. The two-hybrid system: a method to identify and clone genes for proteins that interact with a protein of interest.
    Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9578-82 PMID: 1946372
  29. Identification of functionally related genes that stimulate early meiotic gene expression in yeast.
    Genetics. 1993 Jan;133(1):67-77 PMID: 8417990
  30. Genetic evidence for transcriptional activation by the yeast IME1 gene product.
    Genetics. 1993 Apr;133(4):775-84 PMID: 8462841
  31. Catalytic roles of yeast GSK3beta/shaggy homolog Rim11p in meiotic activation.
    Genetics. 1999 Nov;153(3):1145-52 PMID: 10545448
  32. Essential functions of protein tyrosine phosphatases PTP2 and PTP3 and RIM11 tyrosine phosphorylation in Saccharomyces cerevisiae meiosis and sporulation.
    Mol Biol Cell. 2000 Feb;11(2):663-76 PMID: 10679022
  33. Shared roles of yeast glycogen synthase kinase 3 family members in nitrogen-responsive phosphorylation of meiotic regulator Ume6p.
    Mol Cell Biol. 2000 Aug;20(15):5447-53 PMID: 10891485
  34. GSK3, a master switch regulating cell-fate specification and tumorigenesis.
    Curr Opin Genet Dev. 2000 Oct;10(5):508-14 PMID: 10980428
  35. The Isw2 chromatin remodeling complex represses early meiotic genes upon recruitment by Ume6p.
    Cell. 2000 Oct 27;103(3):423-33 PMID: 11081629
  36. A positive regulator of mitosis, Sok2, functions as a negative regulator of meiosis in Saccharomyces cerevisiae.
    Mol Cell Biol. 2001 Mar;21(5):1603-12 PMID: 11238897
  37. A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation.
    Mol Cell. 2001 Jun;7(6):1321-7 PMID: 11430833
  38. Regulation of GSK-3: a cellular multiprocessor.
    Cell. 2001 Jun 29;105(7):821-4 PMID: 11439177
  39. Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition.
    Cell. 2001 Jun 15;105(6):721-32 PMID: 11440715
  40. GSK3 takes centre stage more than 20 years after its discovery.
    Biochem J. 2001 Oct 1;359(Pt 1):1-16 PMID: 11563964
  41. The renaissance of GSK3.
    Nat Rev Mol Cell Biol. 2001 Oct;2(10):769-76 PMID: 11584304
  42. Ime2, a meiosis-specific kinase in yeast, is required for destabilization of its transcriptional activator, Ime1.
    Mol Cell Biol. 2002 Apr;22(7):2047-56 PMID: 11884593
  43. Post-transcriptional regulation of IME1 determines initiation of meiosis in Saccharomyces cerevisiae.
    Mol Gen Genet. 1993 Mar;237(3):375-84 PMID: 8483452
  44. MDS1, a dosage suppressor of an mck1 mutant, encodes a putative yeast homolog of glycogen synthase kinase 3.
    Mol Cell Biol. 1994 Jan;14(1):831-9 PMID: 8264650
  45. The B subunit of the DNA polymerase alpha-primase complex in Saccharomyces cerevisiae executes an essential function at the initial stage of DNA replication.
    Mol Cell Biol. 1994 Feb;14(2):923-33 PMID: 8289832
  46. Glycogen synthase kinase-3 beta is a dual specificity kinase differentially regulated by tyrosine and serine/threonine phosphorylation.
    J Biol Chem. 1994 May 20;269(20):14566-74 PMID: 7514173
  47. IME1 gene encodes a transcription factor which is required to induce meiosis in Saccharomyces cerevisiae.
    Dev Genet. 1994;15(2):139-47 PMID: 8205723
  48. UME6 is a key regulator of nitrogen repression and meiotic development.
    Genes Dev. 1994 Apr 1;8(7):796-810 PMID: 7926768
  49. Analysis of RIM11, a yeast protein kinase that phosphorylates the meiotic activator IME1.
    Mol Cell Biol. 1994 Dec;14(12):7909-19 PMID: 7969131
  50. Cell cycle-dependent phosphorylation and dephosphorylation of the yeast DNA polymerase alpha-primase B subunit.
    Mol Cell Biol. 1995 Feb;15(2):883-91 PMID: 7823954
  51. Genetic interactions between SIN3 mutations and the Saccharomyces cerevisiae transcriptional activators encoded by MCM1, STE12, and SWI1.
    Mol Gen Genet. 1994 Dec 15;245(6):675-85 PMID: 7830715
  52. Positive control of yeast meiotic genes by the negative regulator UME6.
    Mol Cell Biol. 1995 Jun;15(6):2955-61 PMID: 7760793
  53. Studies on the transformation of intact yeast cells by the LiAc/SS-DNA/PEG procedure.
    Yeast. 1995 Apr 15;11(4):355-60 PMID: 7785336
  54. UME6, a negative regulator of meiosis in Saccharomyces cerevisiae, contains a C-terminal Zn2Cys6 binuclear cluster that binds the URS1 DNA sequence in a zinc-dependent manner.
    Protein Sci. 1995 Sep;4(9):1832-43 PMID: 8528081
  55. UME6 is a central component of a developmental regulatory switch controlling meiosis-specific gene expression.
    Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12490-4 PMID: 8618927
  56. Stimulation of yeast meiotic gene expression by the glucose-repressible protein kinase Rim15p.
    Mol Cell Biol. 1997 May;17(5):2688-97 PMID: 9111339
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
2004-08-00
Pages
6967-79
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC479714
Subset
IM
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