Functional Identification of Regulatory Elements within the Promoter Region of Platelet-Derived Growth Factor 2

Pech, Michael and Rao, C Durga and Robbins, Keith C and Aaronson, Stuart A (1989) Functional Identification of Regulatory Elements within the Promoter Region of Platelet-Derived Growth Factor 2. In: Molecular and Cellular Biology, 9 (2). pp. 396-405.

PDF Functional_Identification_of_Regulatory.pdf - Published Version Restricted to Registered users only Download (2MB) | Request a copy

Abstract

Human platelet-derived growth factor (PDGF) is composed of two polypeptide chains, PDGF-1 and PDGF-2,the human homolog of the v-sis oncogene. Deregulation of PDGF-2 expression can confer a growth advantage to cells possessing the cognate receptor and, thus, may contribute to the malignant phenotype. We investigated the regulation of PDGF-2 mRNA expression during megakaryocytic differentiation of K562 cells. Induction by 12-O-tetradecanoylphorbol-13-acetate (TPA) led to a greater than 200-fold increase in PDGF-2 transcript levels in these cells. Induction was dependent on protein synthesis and was not enhanced by cycloheximide exposure.In our initial investigation of the PDGF-2 promoter, a minimal promoter region, which included sequences extending only 42 base pairs upstream of the TATA signal, was found to be as efficient as 4 kilobase pairs upstream of the TATA signal in driving expression of a reporter gene in uninduced K562 cells. We also functionally identified different regulatory sequence elements of the PDGF-2 promoter in TPA-induced K562 cells. One region acted as a transcriptional silencer, while another region was necessary for maximal activity of the promoter in megakaryoblasts. This region was shown to bind nuclear factors and was the target for trans-activation in normal and tumor cells. In one tumor cell line, which expressed high PDGF-2 mRNA levels, the presence of the positive regulatory region resulted in a 30-fold increase in promoter activity. However, the ability of the minimal PDGF-2 promoter to drive reporter gene expression in uninduced K562 cells and normal fibroblasts, which contained no detectable PDGF-2 transcripts, implies the existence of other negative control mechanisms beyond the regulation of promoter activity.

Item Type:	Journal Article
Publication:	Molecular and Cellular Biology
Publisher:	American Society for Microbiology
Additional Information:	Copyright of this article belongs to American Society for Microbiology.
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	14 Oct 2010 07:53
Last Modified:	22 Feb 2012 06:18
URI:	http://eprints.iisc.ac.in/id/eprint/33178

Actions (login required)

View Item