Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1997 Dec;17(12):7230–7236. doi: 10.1128/mcb.17.12.7230

Interaction of yeast repressor-activator protein Ume6p with glycogen synthase kinase 3 homolog Rim11p.

K Malathi 1, Y Xiao 1, A P Mitchell 1
PMCID: PMC232580  PMID: 9372955

Abstract

Meiosis and expression of early meiotic genes in the budding yeast Saccharomyces cerevisiae depend upon Rim11p, Ume6p, and Ime1p. Rim11p (also called Mds1p and ScGSK3) is a protein kinase related to glycogen synthase kinase 3 (GSK3); Ume6p is an architectural transcription factor; and Imelp is a Ume6p-binding protein that provides a transcriptional activation domain. Rim11p is required for Ime1p-Ume6p interaction, and prior studies have shown that Rim11p binds to and phosphorylates Ime1p. We show here that Rim11p binds to and phosphorylates Ume6p, as well. Amino acid substitutions in Ume6p that alter a consensus GSK3 site reduce or abolish Rim11p-Ume6p interaction and Rim11p-dependent phosphorylation, and they cause defects in interaction between Ume6p and Ime1p and in meiotic gene expression. Therefore, interaction between Rim11p and Ume6p, resulting in phosphorylation of Ume6p, is required for Ime1p-Ume6p complex formation. Rim11p, like metazoan GSK3beta, phosphorylates both interacting subunits of a target protein complex.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Behrens J., von Kries J. P., Kühl M., Bruhn L., Wedlich D., Grosschedl R., Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996 Aug 15;382(6592):638–642. doi: 10.1038/382638a0. [DOI] [PubMed] [Google Scholar]
  2. Bianchi M. W., Plyte S. E., Kreis M., Woodgett J. R. A Saccharomyces cerevisiae protein-serine kinase related to mammalian glycogen synthase kinase-3 and the Drosophila melanogaster gene shaggy product. Gene. 1993 Nov 30;134(1):51–56. doi: 10.1016/0378-1119(93)90173-z. [DOI] [PubMed] [Google Scholar]
  3. Bowdish K. S., Mitchell A. P. Bipartite structure of an early meiotic upstream activation sequence from Saccharomyces cerevisiae. Mol Cell Biol. 1993 Apr;13(4):2172–2181. doi: 10.1128/mcb.13.4.2172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bowdish K. S., Yuan H. E., Mitchell A. P. Analysis of RIM11, a yeast protein kinase that phosphorylates the meiotic activator IME1. Mol Cell Biol. 1994 Dec;14(12):7909–7919. doi: 10.1128/mcb.14.12.7909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bowdish K. S., Yuan H. E., Mitchell A. P. Positive control of yeast meiotic genes by the negative regulator UME6. Mol Cell Biol. 1995 Jun;15(6):2955–2961. doi: 10.1128/mcb.15.6.2955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cross D. A., Alessi D. R., Cohen P., Andjelkovich M., Hemmings B. A. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995 Dec 21;378(6559):785–789. doi: 10.1038/378785a0. [DOI] [PubMed] [Google Scholar]
  7. Durfee T., Becherer K., Chen P. L., Yeh S. H., Yang Y., Kilburn A. E., Lee W. H., Elledge S. J. The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit. Genes Dev. 1993 Apr;7(4):555–569. doi: 10.1101/gad.7.4.555. [DOI] [PubMed] [Google Scholar]
  8. Estojak J., Brent R., Golemis E. A. Correlation of two-hybrid affinity data with in vitro measurements. Mol Cell Biol. 1995 Oct;15(10):5820–5829. doi: 10.1128/mcb.15.10.5820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gibbs C. S., Zoller M. J. Rational scanning mutagenesis of a protein kinase identifies functional regions involved in catalysis and substrate interactions. J Biol Chem. 1991 May 15;266(14):8923–8931. [PubMed] [Google Scholar]
  10. Honigberg S. M., McCarroll R. M., Esposito R. E. Regulatory mechanisms in meiosis. Curr Opin Cell Biol. 1993 Apr;5(2):219–225. doi: 10.1016/0955-0674(93)90106-z. [DOI] [PubMed] [Google Scholar]
  11. Hughes K., Nikolakaki E., Plyte S. E., Totty N. F., Woodgett J. R. Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation. EMBO J. 1993 Feb;12(2):803–808. doi: 10.1002/j.1460-2075.1993.tb05715.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Insall R. Glycogen synthase kinase and Dictyostelium development: old pathways pointing in new directions? Trends Genet. 1995 Feb;11(2):37–39. doi: 10.1016/s0168-9525(00)88989-1. [DOI] [PubMed] [Google Scholar]
  13. Jackson J. C., Lopes J. M. The yeast UME6 gene is required for both negative and positive transcriptional regulation of phospholipid biosynthetic gene expression. Nucleic Acids Res. 1996 Apr 1;24(7):1322–1329. doi: 10.1093/nar/24.7.1322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Johnson L. N., Noble M. E., Owen D. J. Active and inactive protein kinases: structural basis for regulation. Cell. 1996 Apr 19;85(2):149–158. doi: 10.1016/s0092-8674(00)81092-2. [DOI] [PubMed] [Google Scholar]
  15. Kadosh D., Struhl K. Repression by Ume6 involves recruitment of a complex containing Sin3 corepressor and Rpd3 histone deacetylase to target promoters. Cell. 1997 May 2;89(3):365–371. doi: 10.1016/s0092-8674(00)80217-2. [DOI] [PubMed] [Google Scholar]
  16. Kane S. M., Roth R. Carbohydrate metabolism during ascospore development in yeast. J Bacteriol. 1974 Apr;118(1):8–14. doi: 10.1128/jb.118.1.8-14.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Knighton D. R., Zheng J. H., Ten Eyck L. F., Xuong N. H., Taylor S. S., Sowadski J. M. Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science. 1991 Jul 26;253(5018):414–420. doi: 10.1126/science.1862343. [DOI] [PubMed] [Google Scholar]
  18. Mandel S., Robzyk K., Kassir Y. IME1 gene encodes a transcription factor which is required to induce meiosis in Saccharomyces cerevisiae. Dev Genet. 1994;15(2):139–147. doi: 10.1002/dvg.1020150204. [DOI] [PubMed] [Google Scholar]
  19. Mitchell A. P., Bowdish K. S. Selection for early meiotic mutants in yeast. Genetics. 1992 May;131(1):65–72. doi: 10.1093/genetics/131.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mitchell A. P. Control of meiotic gene expression in Saccharomyces cerevisiae. Microbiol Rev. 1994 Mar;58(1):56–70. doi: 10.1128/mr.58.1.56-70.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mitchell D. A., Marshall T. K., Deschenes R. J. Vectors for the inducible overexpression of glutathione S-transferase fusion proteins in yeast. Yeast. 1993 Jul;9(7):715–722. doi: 10.1002/yea.320090705. [DOI] [PubMed] [Google Scholar]
  22. Molenaar M., van de Wetering M., Oosterwegel M., Peterson-Maduro J., Godsave S., Korinek V., Roose J., Destrée O., Clevers H. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 1996 Aug 9;86(3):391–399. doi: 10.1016/s0092-8674(00)80112-9. [DOI] [PubMed] [Google Scholar]
  23. Moon R. T., Brown J. D., Torres M. WNTs modulate cell fate and behavior during vertebrate development. Trends Genet. 1997 Apr;13(4):157–162. doi: 10.1016/s0168-9525(97)01093-7. [DOI] [PubMed] [Google Scholar]
  24. Morin P. J., Sparks A. B., Korinek V., Barker N., Clevers H., Vogelstein B., Kinzler K. W. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997 Mar 21;275(5307):1787–1790. doi: 10.1126/science.275.5307.1787. [DOI] [PubMed] [Google Scholar]
  25. Park H. D., Luche R. M., Cooper T. G. The yeast UME6 gene product is required for transcriptional repression mediated by the CAR1 URS1 repressor binding site. Nucleic Acids Res. 1992 Apr 25;20(8):1909–1915. doi: 10.1093/nar/20.8.1909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Puziss J. W., Hardy T. A., Johnson R. B., Roach P. J., Hieter P. 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):831–839. doi: 10.1128/mcb.14.1.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Roach P. J. Multisite and hierarchal protein phosphorylation. J Biol Chem. 1991 Aug 5;266(22):14139–14142. [PubMed] [Google Scholar]
  28. Roeder G. S. Sex and the single cell: meiosis in yeast. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10450–10456. doi: 10.1073/pnas.92.23.10450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rothstein R. Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast. Methods Enzymol. 1991;194:281–301. doi: 10.1016/0076-6879(91)94022-5. [DOI] [PubMed] [Google Scholar]
  30. Rubin-Bejerano I., Mandel S., Robzyk K., Kassir Y. 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):2518–2526. doi: 10.1128/mcb.16.5.2518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rubinfeld B., Albert I., Porfiri E., Fiol C., Munemitsu S., Polakis P. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science. 1996 May 17;272(5264):1023–1026. doi: 10.1126/science.272.5264.1023. [DOI] [PubMed] [Google Scholar]
  32. Sia R. A., Mitchell A. P. Stimulation of later functions of the yeast meiotic protein kinase Ime2p by the IDS2 gene product. Mol Cell Biol. 1995 Oct;15(10):5279–5287. doi: 10.1128/mcb.15.10.5279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sikorski R. S., Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Smith H. E., Driscoll S. E., Sia R. A., Yuan H. E., Mitchell A. P. Genetic evidence for transcriptional activation by the yeast IME1 gene product. Genetics. 1993 Apr;133(4):775–784. doi: 10.1093/genetics/133.4.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Smith H. E., Su S. S., Neigeborn L., Driscoll S. E., Mitchell A. P. Role of IME1 expression in regulation of meiosis in Saccharomyces cerevisiae. Mol Cell Biol. 1990 Dec;10(12):6103–6113. doi: 10.1128/mcb.10.12.6103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Steber C. M., Esposito R. E. 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):12490–12494. doi: 10.1073/pnas.92.26.12490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Strich R., Surosky R. T., Steber C., Dubois E., Messenguy F., Esposito R. E. UME6 is a key regulator of nitrogen repression and meiotic development. Genes Dev. 1994 Apr 1;8(7):796–810. doi: 10.1101/gad.8.7.796. [DOI] [PubMed] [Google Scholar]
  38. Su S. S., Mitchell A. P. Identification of functionally related genes that stimulate early meiotic gene expression in yeast. Genetics. 1993 Jan;133(1):67–77. doi: 10.1093/genetics/133.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Taylor S. S., Knighton D. R., Zheng J., Sowadski J. M., Gibbs C. S., Zoller M. J. A template for the protein kinase family. Trends Biochem Sci. 1993 Mar;18(3):84–89. doi: 10.1016/0968-0004(93)80001-r. [DOI] [PubMed] [Google Scholar]
  40. Tyers M., Tokiwa G., Futcher B. Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins. EMBO J. 1993 May;12(5):1955–1968. doi: 10.1002/j.1460-2075.1993.tb05845.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Vidan S., Mitchell A. P. Stimulation of yeast meiotic gene expression by the glucose-repressible protein kinase Rim15p. Mol Cell Biol. 1997 May;17(5):2688–2697. doi: 10.1128/mcb.17.5.2688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wang Q. M., Fiol C. J., DePaoli-Roach A. A., Roach P. J. 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):14566–14574. [PubMed] [Google Scholar]
  43. Woodgett J. R. Regulation and functions of the glycogen synthase kinase-3 subfamily. Semin Cancer Biol. 1994 Aug;5(4):269–275. [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES