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Gene Review

CTK1  -  Ctk1p

Saccharomyces cerevisiae S288c

Synonyms: CTD kinase 58 kDa subunit, CTD kinase subunit 1, CTD kinase subunit alpha, CTDK-I subunit alpha, YKL139W
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Disease relevance of CTK1


High impact information on CTK1

  • In support, chromatin immunoprecipitation assays demonstrate the presence of Set2 methylation in the coding regions, as well as promoters, of genes regulated by Ctk1 or Set2 [2].
  • Opposing effects of Ctk1 kinase and Fcp1 phosphatase at Ser 2 of the RNA polymerase II C-terminal domain [3].
  • Here we show that the elongation-associated phosphorylation of Ser 2 is dependent upon the Ctk1 kinase, a putative yeast homolog of Cdk9/P-TEFb [3].
  • Serine 2 is phosphorylated during elongation by the Ctk1 kinase, a protein similar to mammalian Cdk9/P-TEFb [4].
  • A genetic screen for suppressors of loss of yeast CTD kinase I (CTDK-I) function (by deletion of the catalytic subunit gene CTK1) identified PTI1, a potential 3' cleavage/polyadenylation factor [5].

Biological context of CTK1

  • Deletion of CTK1, encoding an RNAPII CTD kinase, prevents Lys36 methylation and Set2 recruitment, suggesting that methylation may be triggered by contact of the WW domain or C terminus of Set2 with Ser2-phosphorylated CTD [6].
  • We show that deletion of the kinase subunit CTK1 results in an increase in phosphorylation of serine in position 5 (Ser(5)) of the CTD repeat (Tyr(1)-Ser(2)-Pro(3)-Thr(4)-Ser(5)-Pro(6)-Ser(7)) during logarithmic growth [7].
  • The CTK1 gene product contains a central domain homologous to catalytic subunits of other protein kinases, notably yeast CDC28, suggesting that the 58 kDa subunit is catalytic [8].
  • The 3'-end of the 6472 bp nucleotide sequence overlaps with the upstream region of the previously identified CTK1 gene, encoding the largest subunit of CTD kinase (Lee, J.M. and Greenleaf, A.L., 1991, Gene Expression 2, 149-167), thereby increasing the number of genes on the 8.2 kb fragment to at least five [9].
  • We show that mutation of CTK1, encoding the cdk subunit, causes defects in transcriptional repression by LexA-Tup1 and in transcriptional activation [10].

Associations of CTK1 with chemical compounds

  • We show in the two-hybrid system that Ctk1 interacts with Snf1, a kinase regulating glucose-dependent genes [11].
  • Whereas histone H3K4 trimethylation normally marks 5' ends of highly transcribed genes, under 'transcriptional stress' induced by 6-azauracil (6-AU) and inactivation of pol II, TFIIE or CTD kinases Kin28 and Ctk1, this mark shifted to the 3' end of the TEF1 gene [12].

Physical interactions of CTK1

  • BUR1 mutants are sensitive to the drugs 6-azauracil and mycophenolic acid and interact genetically with the elongation factors Ctk1 and Spt5 [13].
  • We also show that Gbp2 and Hrb1 interact with Ctk1, a kinase that phosphorylates the C-terminal domain of RNA polymerase II during transcription elongation [14].

Enzymatic interactions of CTK1


Regulatory relationships of CTK1

  • Temperature-sensitive alleles of NAB3 are suppressed by deletion of CTK1, a kinase that has been shown to phosphorylate the CTD and increase elongation efficiency in vitro [16].
  • Phosphorylation by Cak1 regulates the C-terminal domain kinase Ctk1 in Saccharomyces cerevisiae [15].
  • These findings reveal a mechanism by which H2B ubiquitylation acts as a barrier to Ctk1 association with active genes, while subsequent deubiquitylation by Ubp8 triggers Ctk1 recruitment at the appropriate point in activation [17].

Other interactions of CTK1

  • We have now cloned the genes for the two smaller kinase subunits, CTK2 and CTK3, and found that they form a unique, divergent cyclin-cyclin-dependent kinase complex with the previously characterized largest subunit protein CTK1, a cyclin-dependent kinase homolog [18].
  • Although genetic interactions were identified between ESS1 and all four kinases, the clearest interactions were with CTK1 and SRB10 [19].
  • Here we demonstrate that deletion of the CTK1 gene, encoding the kinase subunit of RNA polymerase II carboxy-terminal domain kinase I (CTDK-I), is synthetically lethal when combined with deletion of PPR2 or ELP genes [20].
  • Northern blot analysis suggested that Ctk1 and Snf1 act together in vivo to regulate GSY2 [11].
  • Therefore, Ctk1 phosphorylation on Thr-338 is carried out by Cak1 and is required for normal gene transcription during the transition into stationary phase [15].


  1. Defects in yeast RNA polymerase II transcription elicit hypersensitivity to G1 arrest induced by Kluyveromyces lactis zymocin. Kitamoto, H.K., Jablonowski, D., Nagase, J., Schaffrath, R. Mol. Genet. Genomics (2002) [Pubmed]
  2. Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast. Xiao, T., Hall, H., Kizer, K.O., Shibata, Y., Hall, M.C., Borchers, C.H., Strahl, B.D. Genes Dev. (2003) [Pubmed]
  3. Opposing effects of Ctk1 kinase and Fcp1 phosphatase at Ser 2 of the RNA polymerase II C-terminal domain. Cho, E.J., Kobor, M.S., Kim, M., Greenblatt, J., Buratowski, S. Genes Dev. (2001) [Pubmed]
  4. Phosphorylation of serine 2 within the RNA polymerase II C-terminal domain couples transcription and 3' end processing. Ahn, S.H., Kim, M., Buratowski, S. Mol. Cell (2004) [Pubmed]
  5. The RNA polymerase II CTD kinase CTDK-I affects pre-mRNA 3' cleavage/polyadenylation through the processing component Pti1p. Skaar, D.A., Greenleaf, A.L. Mol. Cell (2002) [Pubmed]
  6. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Krogan, N.J., Kim, M., Tong, A., Golshani, A., Cagney, G., Canadien, V., Richards, D.P., Beattie, B.K., Emili, A., Boone, C., Shilatifard, A., Buratowski, S., Greenblatt, J. Mol. Cell. Biol. (2003) [Pubmed]
  7. Yeast carboxyl-terminal domain kinase I positively and negatively regulates RNA polymerase II carboxyl-terminal domain phosphorylation. Patturajan, M., Conrad, N.K., Bregman, D.B., Corden, J.L. J. Biol. Chem. (1999) [Pubmed]
  8. CTD kinase large subunit is encoded by CTK1, a gene required for normal growth of Saccharomyces cerevisiae. Lee, J.M., Greenleaf, A.L. Gene Expr. (1991) [Pubmed]
  9. Molecular cloning and physical analysis of an 8.2 kb segment of chromosome XI of Saccharomyces cerevisiae reveals five tightly linked genes. Abraham, P.R., Mulder, A., Van 't Riet, J., Planta, R.J., Raué, H.A. Yeast (1992) [Pubmed]
  10. Functional relationships of Srb10-Srb11 kinase, carboxy-terminal domain kinase CTDK-I, and transcriptional corepressor Ssn6-Tup1. Kuchin, S., Carlson, M. Mol. Cell. Biol. (1998) [Pubmed]
  11. Glucose deprivation mediates interaction between CTDK-I and Snf1 in Saccharomyces cerevisiae. Van Driessche, B., Coddens, S., Van Mullem, V., Vandenhaute, J. FEBS Lett. (2005) [Pubmed]
  12. Altered nucleosome occupancy and histone H3K4 methylation in response to 'transcriptional stress'. Zhang, L., Schroeder, S., Fong, N., Bentley, D.L. EMBO J. (2005) [Pubmed]
  13. Bur1 kinase is required for efficient transcription elongation by RNA polymerase II. Keogh, M.C., Podolny, V., Buratowski, S. Mol. Cell. Biol. (2003) [Pubmed]
  14. Cotranscriptional recruitment of the serine-arginine-rich (SR)-like proteins Gbp2 and Hrb1 to nascent mRNA via the TREX complex. Hurt, E., Luo, M.J., Röther, S., Reed, R., Strässer, K. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  15. Phosphorylation by Cak1 regulates the C-terminal domain kinase Ctk1 in Saccharomyces cerevisiae. Ostapenko, D., Solomon, M.J. Mol. Cell. Biol. (2005) [Pubmed]
  16. A yeast heterogeneous nuclear ribonucleoprotein complex associated with RNA polymerase II. Conrad, N.K., Wilson, S.M., Steinmetz, E.J., Patturajan, M., Brow, D.A., Swanson, M.S., Corden, J.L. Genetics (2000) [Pubmed]
  17. H2B ubiquitylation acts as a barrier to Ctk1 nucleosomal recruitment prior to removal by Ubp8 within a SAGA-related complex. Wyce, A., Xiao, T., Whelan, K.A., Kosman, C., Walter, W., Eick, D., Hughes, T.R., Krogan, N.J., Strahl, B.D., Berger, S.L. Mol. Cell (2007) [Pubmed]
  18. The yeast carboxyl-terminal repeat domain kinase CTDK-I is a divergent cyclin-cyclin-dependent kinase complex. Sterner, D.E., Lee, J.M., Hardin, S.E., Greenleaf, A.L. Mol. Cell. Biol. (1995) [Pubmed]
  19. Genetic interactions with C-terminal domain (CTD) kinases and the CTD of RNA Pol II suggest a role for ESS1 in transcription initiation and elongation in Saccharomyces cerevisiae. Wilcox, C.B., Rossettini, A., Hanes, S.D. Genetics (2004) [Pubmed]
  20. Involvement of yeast carboxy-terminal domain kinase I (CTDK-I) in transcription elongation in vivo. Jona, G., Wittschieben, B.O., Svejstrup, J.Q., Gileadi, O. Gene (2001) [Pubmed]
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