Skip to main content
NCBI home page
The EMBO Journal logoLink to The EMBO Journal
. 1997 Sep 1;16(17):5289–5298. doi: 10.1093/emboj/16.17.5289

DBF2, a cell cycle-regulated protein kinase, is physically and functionally associated with the CCR4 transcriptional regulatory complex.

H Y Liu 1, J H Toyn 1, Y C Chiang 1, M P Draper 1, L H Johnston 1, C L Denis 1
PMCID: PMC1170161  PMID: 9311989

Abstract

CCR4, a general transcriptional regulator affecting the expression of a number of genes in yeast, forms a multi-subunit complex in vivo. Using the yeast two-hybrid screen, we have identified DBF2, a cell cycle-regulated protein kinase, as a CCR4-associated protein. DBF2 is required for cell cycle progression at the telophase to G1 cell cycle transition. DBF2 co-immunoprecipitated with CCR4 and CAF1/POP2, a CCR4-associated factor, and co-purified with the CCR4 complex. Moreover, a dbf2 disruption resulted in phenotypes and transcriptional defects similar to those observed in strains deficient for CCR4 or CAF1. ccr4 and caf1 mutations, on the other hand, were found to affect cell cycle progression in a manner similar to that observed for dbf2 defects. These data indicate that DBF2 is involved in the control of gene expression and suggest that the CCR4 complex regulates transcription during the late mitotic part of the cell cycle.

Full Text

The Full Text of this article is available as a PDF (279.1 KB).

Selected References

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

  1. Costigan C., Kolodrubetz D., Snyder M. NHP6A and NHP6B, which encode HMG1-like proteins, are candidates for downstream components of the yeast SLT2 mitogen-activated protein kinase pathway. Mol Cell Biol. 1994 Apr;14(4):2391–2403. doi: 10.1128/mcb.14.4.2391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Denis C. L. Identification of new genes involved in the regulation of yeast alcohol dehydrogenase II. Genetics. 1984 Dec;108(4):833–844. doi: 10.1093/genetics/108.4.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Denis C. L., Malvar T. The CCR4 gene from Saccharomyces cerevisiae is required for both nonfermentative and spt-mediated gene expression. Genetics. 1990 Feb;124(2):283–291. doi: 10.1093/genetics/124.2.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dollard C., Ricupero-Hovasse S. L., Natsoulis G., Boeke J. D., Winston F. SPT10 and SPT21 are required for transcription of particular histone genes in Saccharomyces cerevisiae. Mol Cell Biol. 1994 Aug;14(8):5223–5228. doi: 10.1128/mcb.14.8.5223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Donovan J. D., Toyn J. H., Johnson A. L., Johnston L. H. P40SDB25, a putative CDK inhibitor, has a role in the M/G1 transition in Saccharomyces cerevisiae. Genes Dev. 1994 Jul 15;8(14):1640–1653. doi: 10.1101/gad.8.14.1640. [DOI] [PubMed] [Google Scholar]
  6. Draper M. P., Liu H. Y., Nelsbach A. H., Mosley S. P., Denis C. L. CCR4 is a glucose-regulated transcription factor whose leucine-rich repeat binds several proteins important for placing CCR4 in its proper promoter context. Mol Cell Biol. 1994 Jul;14(7):4522–4531. doi: 10.1128/mcb.14.7.4522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Draper M. P., Salvadore C., Denis C. L. Identification of a mouse protein whose homolog in Saccharomyces cerevisiae is a component of the CCR4 transcriptional regulatory complex. Mol Cell Biol. 1995 Jul;15(7):3487–3495. doi: 10.1128/mcb.15.7.3487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hengartner C. J., Thompson C. M., Zhang J., Chao D. M., Liao S. M., Koleske A. J., Okamura S., Young R. A. Association of an activator with an RNA polymerase II holoenzyme. Genes Dev. 1995 Apr 15;9(8):897–910. doi: 10.1101/gad.9.8.897. [DOI] [PubMed] [Google Scholar]
  9. Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Johnston L. H., Eberly S. L., Chapman J. W., Araki H., Sugino A. The product of the Saccharomyces cerevisiae cell cycle gene DBF2 has homology with protein kinases and is periodically expressed in the cell cycle. Mol Cell Biol. 1990 Apr;10(4):1358–1366. doi: 10.1128/mcb.10.4.1358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lee K. S., Hines L. K., Levin D. E. A pair of functionally redundant yeast genes (PPZ1 and PPZ2) encoding type 1-related protein phosphatases function within the PKC1-mediated pathway. Mol Cell Biol. 1993 Sep;13(9):5843–5853. doi: 10.1128/mcb.13.9.5843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Malvar T., Biron R. W., Kaback D. B., Denis C. L. The CCR4 protein from Saccharomyces cerevisiae contains a leucine-rich repeat region which is required for its control of ADH2 gene expression. Genetics. 1992 Dec;132(4):951–962. doi: 10.1093/genetics/132.4.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McKenzie E. A., Kent N. A., Dowell S. J., Moreno F., Bird L. E., Mellor J. The centromere and promoter factor, 1, CPF1, of Saccharomyces cerevisiae modulates gene activity through a family of factors including SPT21, RPD1 (SIN3), RPD3 and CCR4. Mol Gen Genet. 1993 Sep;240(3):374–386. doi: 10.1007/BF00280389. [DOI] [PubMed] [Google Scholar]
  14. Natsoulis G., Dollard C., Winston F., Boeke J. D. The products of the SPT10 and SPT21 genes of Saccharomyces cerevisiae increase the amplitude of transcriptional regulation at a large number of unlinked loci. New Biol. 1991 Dec;3(12):1249–1259. [PubMed] [Google Scholar]
  15. Posas F., Casamayor A., Ariño J. The PPZ protein phosphatases are involved in the maintenance of osmotic stability of yeast cells. FEBS Lett. 1993 Mar 8;318(3):282–286. doi: 10.1016/0014-5793(93)80529-4. [DOI] [PubMed] [Google Scholar]
  16. Roemer T., Paravicini G., Payton M. A., Bussey H. Characterization of the yeast (1-->6)-beta-glucan biosynthetic components, Kre6p and Skn1p, and genetic interactions between the PKC1 pathway and extracellular matrix assembly. J Cell Biol. 1994 Oct;127(2):567–579. doi: 10.1083/jcb.127.2.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sakai A., Chibazakura T., Shimizu Y., Hishinuma F. Molecular analysis of POP2 gene, a gene required for glucose-derepression of gene expression in Saccharomyces cerevisiae. Nucleic Acids Res. 1992 Dec 11;20(23):6227–6233. doi: 10.1093/nar/20.23.6227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schild D. Suppression of a new allele of the yeast RAD52 gene by overexpression of RAD51, mutations in srs2 and ccr4, or mating-type heterozygosity. Genetics. 1995 May;140(1):115–127. doi: 10.1093/genetics/140.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Shimizu J., Yoda K., Yamasaki M. The hypo-osmolarity-sensitive phenotype of the Saccharomyces cerevisiae hpo2 mutant is due to a mutation in PKC1, which regulates expression of beta-glucanase. Mol Gen Genet. 1994 Mar;242(6):641–648. doi: 10.1007/BF00283417. [DOI] [PubMed] [Google Scholar]
  20. Shirayama M., Matsui Y., Toh-E A. The yeast TEM1 gene, which encodes a GTP-binding protein, is involved in termination of M phase. Mol Cell Biol. 1994 Nov;14(11):7476–7482. doi: 10.1128/mcb.14.11.7476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Surana U., Amon A., Dowzer C., McGrew J., Byers B., Nasmyth K. Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast. EMBO J. 1993 May;12(5):1969–1978. doi: 10.1002/j.1460-2075.1993.tb05846.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Toyn J. H., Araki H., Sugino A., Johnston L. H. The cell-cycle-regulated budding yeast gene DBF2, encoding a putative protein kinase, has a homologue that is not under cell-cycle control. Gene. 1991 Jul 31;104(1):63–70. doi: 10.1016/0378-1119(91)90465-n. [DOI] [PubMed] [Google Scholar]
  23. Toyn J. H., Johnson A. L., Donovan J. D., Toone W. M., Johnston L. H. The Swi5 transcription factor of Saccharomyces cerevisiae has a role in exit from mitosis through induction of the cdk-inhibitor Sic1 in telophase. Genetics. 1997 Jan;145(1):85–96. doi: 10.1093/genetics/145.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Toyn J. H., Johnston L. H. Spo12 is a limiting factor that interacts with the cell cycle protein kinases Dbf2 and Dbf20, which are involved in mitotic chromatid disjunction. Genetics. 1993 Dec;135(4):963–971. doi: 10.1093/genetics/135.4.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Toyn J. H., Johnston L. H. The Dbf2 and Dbf20 protein kinases of budding yeast are activated after the metaphase to anaphase cell cycle transition. EMBO J. 1994 Mar 1;13(5):1103–1113. doi: 10.1002/j.1460-2075.1994.tb06359.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Vallari R. C., Cook W. J., Audino D. C., Morgan M. J., Jensen D. E., Laudano A. P., Denis C. L. Glucose repression of the yeast ADH2 gene occurs through multiple mechanisms, including control of the protein synthesis of its transcriptional activator, ADR1. Mol Cell Biol. 1992 Apr;12(4):1663–1673. doi: 10.1128/mcb.12.4.1663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Yang X., Hubbard E. J., Carlson M. A protein kinase substrate identified by the two-hybrid system. Science. 1992 Jul 31;257(5070):680–682. doi: 10.1126/science.1496382. [DOI] [PubMed] [Google Scholar]
  28. Zervos A. S., Gyuris J., Brent R. Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell. 1993 Jan 29;72(2):223–232. doi: 10.1016/0092-8674(93)90662-a. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES