Home LiteratureArticle Details
PMID: 9860980 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Differential regulation of transcription: repression by unactivated mitogen-activated protein kinase Kss1 requires the Dig1 and Dig2 proteins.

Bardwell L, Cook JG, Zhu-Shimoni JX, Voora D, Thorner J

Abstract

Kss1, a yeast mitogen-activated protein kinase (MAPK), in its unphosphorylated (unactivated) state binds directly to and represses Ste12, a transcription factor necessary for expression of genes whose promoters contain filamentous response elements (FREs) and genes whose promoters contain pheromone response elements (PREs). Herein we show that two nuclear proteins, Dig1 and Dig2, are required cofactors in Kss1-imposed repression. Dig1 and Dig2 cooperate with Kss1 to repress Ste12 action at FREs and regulate invasive growth in a naturally invasive strain. Kss1-imposed Dig-dependent repression of Ste12 also occurs at PREs. However, maintenance of repression at PREs is more dependent on Dig1 and/or Dig2 and less dependent on Kss1 than repression at FREs. In addition, derepression at PREs is more dependent on MAPK-mediated phosphorylation than is derepression at FREs. Differential utilization of two types of MAPK-mediated regulation (binding-imposed repression and phosphorylation-dependent activation), in combination with distinct Ste12-containing complexes, contributes to the mechanisms by which separate extracellular stimuli that use the same MAPK cascade can elicit two different transcriptional responses.

MeSH Terms
Calcium-Calmodulin-Dependent Protein Kinases/metabolism Fungal Proteins/genetics,metabolism Gene Expression Regulation, Fungal Genes, Reporter Genotype Mitogen-Activated Protein Kinases Models, Biological Pheromones/physiology Phosphorylation Promoter Regions, Genetic Recombinant Proteins/metabolism Saccharomyces cerevisiae/genetics,growth & development,metabolism Saccharomyces cerevisiae Proteins Transcription Factors/genetics,metabolism Transcription, Genetic
Chemicals
DIG1 protein, S cerevisiae DIG2 protein, S cerevisiae Fungal Proteins Pheromones Recombinant Proteins STE12 protein, S cerevisiae Saccharomyces cerevisiae Proteins Transcription Factors Calcium-Calmodulin-Dependent Protein Kinases FUS3 protein, S cerevisiae KSS1 protein, S cerevisiae Mitogen-Activated Protein Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bardwell L
Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720, USA.
Cook J G
Zhu-Shimoni J X
Voora D
Thorner J
References (52)
52 references, click to expand
  1. Repression of yeast Ste12 transcription factor by direct binding of unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK.
    Genes Dev. 1998 Sep 15;12(18):2887-98 PMID: 9744865
  2. Putting the HO gene to work: practical uses for mating-type switching.
    Methods Enzymol. 1991;194:132-46 PMID: 2005783
  3. Multiple DNA-protein interactions governing high-precision DNA transactions.
    Science. 1986 Sep 5;233(4768):1050-6 PMID: 2943018
  4. New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites.
    Gene. 1988 Dec 30;74(2):527-34 PMID: 3073106
  5. 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 PMID: 2659436
  6. Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast.
    Methods Enzymol. 1991;194:281-301 PMID: 2005793
  7. Pheromone response elements are necessary and sufficient for basal and pheromone-induced transcription of the FUS1 gene of Saccharomyces cerevisiae.
    Mol Cell Biol. 1991 Jun;11(6):2952-61 PMID: 1903837
  8. Properties of the DNA-binding domain of the Saccharomyces cerevisiae STE12 protein.
    Mol Cell Biol. 1991 Dec;11(12):5910-8 PMID: 1944269
  9. FUS3 represses CLN1 and CLN2 and in concert with KSS1 promotes signal transduction.
    Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9392-6 PMID: 1946350
  10. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS.
    Cell. 1992 Mar 20;68(6):1077-90 PMID: 1547504
  11. A presumptive helicase (MOT1 gene product) affects gene expression and is required for viability in the yeast Saccharomyces cerevisiae.
    Mol Cell Biol. 1992 Apr;12(4):1879-92 PMID: 1312673
  12. Extracellular signal-regulated kinases: ERKs in progress.
    Cell Regul. 1991 Dec;2(12):965-78 PMID: 1801927
  13. Coupling of cell identity to signal response in yeast: interaction between the alpha 1 and STE12 proteins.
    Genes Dev. 1993 Aug;7(8):1584-97 PMID: 8339934
  14. Elements of the yeast pheromone response pathway required for filamentous growth of diploids.
    Science. 1993 Dec 10;262(5140):1741-4 PMID: 8259520
  15. A gain-of-function mutation in Drosophila MAP kinase activates multiple receptor tyrosine kinase signaling pathways.
    Cell. 1994 Mar 11;76(5):875-88 PMID: 8124723
  16. Saccharomyces cerevisiae virulence phenotype as determined with CD-1 mice is associated with the ability to grow at 42 degrees C and form pseudohyphae.
    Infect Immun. 1994 Dec;62(12):5447-55 PMID: 7960125
  17. Elements of a single MAP kinase cascade in Saccharomyces cerevisiae mediate two developmental programs in the same cell type: mating and invasive growth.
    Genes Dev. 1994 Dec 15;8(24):2974-85 PMID: 8001818
  18. Signal propagation and regulation in the mating pheromone response pathway of the yeast Saccharomyces cerevisiae.
    Dev Biol. 1994 Dec;166(2):363-79 PMID: 7813763
  19. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation.
    Cell. 1995 Jan 27;80(2):179-85 PMID: 7834738
  20. Transcriptional regulation by extracellular signals: mechanisms and specificity.
    Cell. 1995 Jan 27;80(2):199-211 PMID: 7834740
  21. Symmetric cell division in pseudohyphae of the yeast Saccharomyces cerevisiae.
    Mol Biol Cell. 1994 Sep;5(9):1003-22 PMID: 7841518
  22. Requirement of MAP kinase for differentiation of fibroblasts to adipocytes, for insulin activation of p90 S6 kinase and for insulin or serum stimulation of DNA synthesis.
    EMBO J. 1995 Feb 15;14(4):674-84 PMID: 7882971
  23. The price of repression.
    Cell. 1995 Jun 2;81(5):655-8 PMID: 7774005
  24. Phosphorylation and localization of Kss1, a MAP kinase of the Saccharomyces cerevisiae pheromone response pathway.
    Mol Biol Cell. 1995 Jul;6(7):889-909 PMID: 7579701
  25. Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1996 May 28;93(11):5352-6 PMID: 8643578
  26. Signaling in the yeast pheromone response pathway: specific and high-affinity interaction of the mitogen-activated protein (MAP) kinases Kss1 and Fus3 with the upstream MAP kinase kinase Ste7.
    Mol Cell Biol. 1996 Jul;16(7):3637-50 PMID: 8668180
  27. Muc1, a mucin-like protein that is regulated by Mss10, is critical for pseudohyphal differentiation in yeast.
    Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8419-24 PMID: 8710886
  28. Transcriptional repression in development.
    Curr Opin Cell Biol. 1996 Jun;8(3):358-64 PMID: 8743887
  29. Regulation of transcription by MAP kinase cascades.
    Curr Opin Cell Biol. 1996 Apr;8(2):205-15 PMID: 8791420
  30. Yeast Saccharomyces cerevisiae selectable markers in pUC18 polylinkers.
    Yeast. 1990 Sep-Oct;6(5):363-6 PMID: 2220072
  31. Cell-type-specific transcription in yeast.
    Biochim Biophys Acta. 1991 Feb 16;1088(2):155-69 PMID: 1900437
  32. Threshold responses to the dorsal regulatory gradient and the subdivision of primary tissue territories in the Drosophila embryo.
    Curr Opin Genet Dev. 1996 Aug;6(4):416-23 PMID: 8791536
  33. Saccharomyces cerevisiae S288C has a mutation in FLO8, a gene required for filamentous growth.
    Genetics. 1996 Nov;144(3):967-78 PMID: 8913742
  34. Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans.
    Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13217-22 PMID: 8917571
  35. Candida albicans strains heterozygous and homozygous for mutations in mitogen-activated protein kinase signaling components have defects in hyphal development.
    Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13223-8 PMID: 8917572
  36. Two novel targets of the MAP kinase Kss1 are negative regulators of invasive growth in the yeast Saccharomyces cerevisiae.
    Genes Dev. 1996 Nov 15;10(22):2831-48 PMID: 8918885
  37. Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs.
    Trends Biochem Sci. 1996 Dec;21(12):460-6 PMID: 9009826
  38. Combinatorial control required for the specificity of yeast MAPK signaling.
    Science. 1997 Feb 28;275(5304):1314-7 PMID: 9036858
  39. Regulation of the mating pheromone and invasive growth responses in yeast by two MAP kinase substrates.
    Curr Biol. 1997 Apr 1;7(4):228-38 PMID: 9094309
  40. Characterization of the basal and pheromone-stimulated phosphorylation states of Ste12p.
    Eur J Biochem. 1997 Apr 15;245(2):241-51 PMID: 9151949
  41. Cooperative binding interactions required for function of the Ty1 sterile responsive element.
    Mol Cell Biol. 1997 Aug;17(8):4330-7 PMID: 9234690
  42. Transcription factors in eye development: a gorgeous mosaic?
    Genes Dev. 1997 Aug 15;11(16):2023-8 PMID: 9284042
  43. Nonfilamentous C. albicans mutants are avirulent.
    Cell. 1997 Sep 5;90(5):939-49 PMID: 9298905
  44. Transcriptional activation upon pheromone stimulation mediated by a small domain of Saccharomyces cerevisiae Ste12p.
    Mol Cell Biol. 1997 Nov;17(11):6410-8 PMID: 9343403
  45. Inhibitory and activating functions for MAPK Kss1 in the S. cerevisiae filamentous-growth signalling pathway.
    Nature. 1997 Nov 6;390(6655):85-8 PMID: 9363895
  46. MAP kinases with distinct inhibitory functions impart signaling specificity during yeast differentiation.
    Cell. 1997 Nov 28;91(5):673-84 PMID: 9393860
  47. The cell surface flocculin Flo11 is required for pseudohyphae formation and invasion by Saccharomyces cerevisiae.
    Mol Biol Cell. 1998 Jan;9(1):161-71 PMID: 9436998
  48. Rap1 mediates sustained MAP kinase activation induced by nerve growth factor.
    Nature. 1998 Apr 9;392(6676):622-6 PMID: 9560161
  49. The riddle of MAP kinase signaling specificity.
    Trends Genet. 1998 Apr;14(4):151-5 PMID: 9594663
  50. Roles of the Candida albicans mitogen-activated protein kinase homolog, Cek1p, in hyphal development and systemic candidiasis.
    Infect Immun. 1998 Jun;66(6):2713-21 PMID: 9596738
  51. Ets transcription factors: nuclear effectors of the Ras-MAP-kinase signaling pathway.
    Trends Biochem Sci. 1998 Jun;23(6):213-6 PMID: 9644975
  52. Fusion of Escherichia coli lacZ to the cytochrome c gene of Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1981 Apr;78(4):2199-203 PMID: 6264467
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1998-12-22
Pages
15400-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC28054
Subset
IM
Grants
NIGMS NIH HHS · R01 GM021841 · United States
NCI NIH HHS · CA09041 · United States
NIGMS NIH HHS · F32 GM019474 · United States
NIGMS NIH HHS · GM21841 · United States
NCI NIH HHS · T32 CA009041 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]