Ets1 is a common element in directing transcription of the α and β genes of human protein kinase CK2

Abstract

Protein kinase CK2 is a conserved and vital Ser/Thr phosphotransferase with various links to malignant diseases, occurring as a tetramer composed of two catalytically active (CK2α and/or CK2α′) and two regulatory subunits (CK2β). There is balanced availability of CK2α and CK2β transcripts in proliferating and differentiating cultured cells. Examination of the human CK2β gene for transcriptionally active regions by systematic deletions and reporter gene assays indicates strong promoter activity at positions −42 to 14 and 12 to 72 containing transcription start sites 1 and 2 of the gene (positions +1 and 33), respectively, an upstream and a downstream enhancer activity at positions −241 to −168 and 123 to 677, respectively, and silencer activity at positions −241 to −261. Of the various transcription factor binding motifs present in those regions, Ets1 and CAAT‐related motifs turned out to be of particular importance, Ets1 for promoter activation and CAAT‐related motifs for enhancer activation. In addition, there are contributions by Sp1. Most strikingly, the Ets1 region representing two adjoining consensus motifs also occurs with complete identity in the recently characterized promoter of the CK2α gene [Krehan, A., Ansuini, H., Böcher, O., Grein, S., Wirkner, U. & Pyerin, W. (2001) J. Biol. Chem.275, 18327–18336], and affects comparably, when assayed in parallel, the promoters of both CK2 genes, both by motif mutations and by Ets1 overexpression. The data strongly support the hypothesis that Ets1 acts as a common regulatory element of the CK2α and CK2β genes involved in directing coordinate transcription and contributing to the balanced availability of transcripts.

Novel mechanism by which histone deacetylase inhibitors facilitate topoisomerase IIα degradation in hepatocellular carcinoma cells

“…ChIP analysis revealed that AR42 treatment caused a concentration-dependent increase in the association of CK2α promoter DNA with acetylated histone H3 (Fig. 4B), which in turn was associated with the enhanced recruitment of the transcription factor Ets-1, a key regulatory element of the CK2α gene (25), to the promoter, without altering the expression level of Ets-1 (Fig. 4C).…”

CK2 kinase activity but not its binding to CK2 promoter regions is implicated in the regulation of CK2α and CK2β gene expressions

“…Previous studies suggested that relevant promoter regions of CK2a, CK2b genes are located within a few hundred base pairs upstream of the transcription start sites. In most of the experiments, even smaller DNA fragments were used for the analysis of transcriptional control [18,56]. Interestingly, the CK2a gene is organized with the first exon located over 35 kb upstream of the second exon, which harbors the start codon.…”

“…Thus, we conclude that SP1 is not the transcription factor which is activated by CK2 for the regulation of the CK2 gene expression. Ets1 is another transcription factor which is supposed to bind to the CK2a promoter [56]. So far, it is not known whether Ets1 is a substrate for CK2.…”

The Multiple Personalities of the Regulatory Subunit of Protein Kinase CK2: CK2 Dependent and CK2 Independent Roles Reveal a Secret Identity for CK2β

“…It is clear that CK2 is involved in cell cycle progression and while it is known that all CK2 subunits are expressed throughout the cell cycle, relatively little is known about how either CK2α or CK2β expression is regulated 72 . Characterization of both the CK2α and CK2β genes, as well as adjacent upstream sequences led to identification of a pair of highly conserved Ets1 response elements 73 , 74 . While these observations offer an attractive mechanism for the coordinated expression of CK2 subunits destined to form tetrameric complexes, these results are not entirely consistent with earlier studies that had shown that CK2β protein was synthesized in excess of the catalytic subunit in exponentially growing tissue culture cells 75 .…”