Disease relevance of CTK1

• The defects at the level of transcriptional elongation displayed by rtf1Delta, ctk1, fcp1 and rpb2 mutants also result in zymocin hypersensitivity [1].

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

• Moreover, Cak1 directly phosphorylated Ctk1 in vitro [15].

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].

References