Ets‐1/ Elk‐1 is a critical mediator of dipeptidyl‐peptidase III transcription in human glioblastoma cells

Abstract

Dipetidyl‐petidase III is a metallopeptidase involved in a number of physiological processes and its expression has been reported to increase with the histological aggressiveness of human ovarian primary carcinomas. Because no information regarding the regulation of its expression was available, experiments were designed to clone, define and characterize the promoter region of the human dipeptidyl‐peptidase III (DPP‐III) gene. In this study, we cloned a 1038 bp 5′‐flanking DNA fragment of the human DPP‐III gene for the first time and demonstrated strong promoter activity in this region. Deletion analysis revealed that as few as 45 nucleotides proximal to the transcription start site retained ∼ 40% of the activity of the full‐length promoter. This promoter lacked the TATA box but contained multiple GC boxes and a single CAAT box. Similarly, two Ets‐1/Elk‐1‐binding motifs are present in the first 25 nucleotides from the transcription start site. Binding of Ets‐1/Elk‐1 proteins to these motifs was visualized by electrophoretic mobility shift and chromatin immunoprecipitation assays. Mutations of these binding sites abolished not only binding of the Ets protein, but also the intrinsic promoter activity. Increased DNA‐binding activity of Ets‐1/Elk‐1 by v‐Ha‐ras also augmented the mRNA level and promoter activity of this gene. Similarly, co‐transfection of DPP‐III promoter–reporter constructs with Ets‐1 expression vector led to a significant increase in promoter activity. From these results, we conclude that Ets‐1/Elk‐1 plays a critical role in transcription of the human DPP‐III gene.

MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication

“…DPP3 is involved in apoptosis modulation and is over-expressed in cancerous cells [58]. RNAi of the DPP3 gene was performed to evaluate the effect on apoptotic gene expression.…”

EGF activates TTP expression by activation of ELK-1 and EGR-1 transcription factors

“…This type of interaction between proteins and DNA enhances the affinity of the second transcription factor, even to the sequence which is not canonical [33,34]. It could not be excluded that ELK-1 forms a complex with other protein from ETS family on the ZFP36 promoter, especially that such complexes were described on other promoters [35-37]. For instance, the formation of heterodimer between Ets-1 and ELK-1 is a key step in the regulation of DPP-III gene expression.…”

Ets1 and Elk1 transcription factors regulatecancerous inhibitor of protein phosphatase 2Aexpression in cervical and endometrial carcinoma cells

“…Interestingly, Ets1 and Elk1 together have recently been identified to regulate the expression of dipeptidyl-peptidase III (DPP-III) gene, which is involved in ovarian cancer aggressivity. 46 CIP2A aids in the development of drug resistance in cancer cells. Recent reports have correlated the overexpression of CIP2A with development of doxorubicin resistance in breast cancer cells (MDA-MB-231) 47 and overexpression of CIP2A in hepatocellular carcinoma cells (HCC) PLC5 leads to resistance to bortezomib.…”