Characterization of the Enhancer-Like Okadaic Acid Response Element Region of the Cyclin-Dependent Kinase 1 (p34cdc2) Promoter

Authors: Liu H.; Bird R.C.

Source: Biochemical and Biophysical Research Communications, Volume 246, Number 3, May 1998 , pp. 696-702(7)

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Abstract:

Expression of the cdk1 (p34cdc2) gene is enhanced 5-10 fold as cells re-enter the cell cycle from quiescence in response to serum-refeeding or following exposure to the protein phosphatase 1/2A inhibitor okadaic acid. Transient transfection analysis of nested deletions of the human cdk1 promoter identified regions that confer sensitivity to okadaic acid on a CAT-reporter gene. Putative okadaic acid response elements (OARE) were located between nt -942 to -763 (Site I) and nt -416 to -186 (Site II) before transcription start. The Site I element has enhancer-like characteristics as activity is independent of sequence orientation. Mobility shift analysis of Site I revealed the presence of 2 high molecular weight complexes, one of which was enhanced in the presence of okadaic acid-treated cell extracts. Site I contained several sequence motifs with conserved homology to heat shock response element core sequences and homeobox protein binding sites. Site II contained a myb-binding site, a G1/S phase enhancer, and 2 retinoblastoma response elements flanking an E2F binding site. Enhancement of cdk1 expression appears dependent on 2 nonhomologous okadaic acid-sensitive promoter regions. Copyright 1998 Academic Press.

Language: English

Document Type: Research article

Affiliations: Department of Pathobiology, Auburn University, Auburn, Alabama, 36849-5519

Publication date: 1998-05-01