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Type: Journal article
Title: Identification of a novel calcitonin-response element in the promoter of the human p21 WAF1/CIP1 gene
Author: Evdokiou, A.
Raggatt, L.
Sakai, T.
Findlay, D.
Citation: Journal of Molecular Endocrinology, 2000; 25(2):195-206
Publisher: Soc Endocrinology
Issue Date: 2000
ISSN: 0952-5041
Abstract: The cyclin-dependent kinase inhibitor p21/WAF1/CIP1 is induced in many cell types in response to a variety of extracellular signals and causes cell cycle arrest in both the G1 and G2/M phases of the cell cycle. We reported previously that calcitonin (CT) receptor (CTR)-mediated growth inhibition of HEK-293 cells stably transfected with the human CTR is accompanied by a rapid and sustained induction of p21 and cell cycle arrest in G2. In the present study we have shown that CT stimulates transcription from a p21 promoter-luciferase construct. Using deletion and mutation analysis of the p21 promoter we have demonstrated that transcriptional activation of p21 by CT is p53-independent and is mediated through specific activation of Sp1-binding sites in a region of the promoter between -82 and -69, relative to the transcription start site. CTR-mediated transcriptional activation of p21 was specific for the insert-negative isoform of the human CTR. Butyrate, which was shown previously to activate the same Sp1 site, synergised with CT to increase further p21 promoter activity. These results provide the first demonstration that CTR can induce gene transcription through the constitutively expressed transcription factor Sp1, and define a mechanism of cell growth suppression that may have implications for other members of the seven-transmembrane domain G protein-coupled receptor superfamily.
Keywords: Cell Line; Humans; Butyrates; Calcitonin; Cyclin-Dependent Kinases; Cyclins; Receptors, Calcitonin; RNA, Messenger; Enzyme Inhibitors; Transfection; DNA Mutational Analysis; Sequence Deletion; Drug Synergism; Sp1 Transcription Factor; Cyclin-Dependent Kinase Inhibitor p21; Promoter Regions, Genetic; Transcriptional Activation
RMID: 0001000676
DOI: 10.1677/jme.0.0250195
Appears in Collections:Orthopaedics and Trauma publications

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