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Suppression of Egr-1 transcription through targeting of the serum response factor by oncogenic H-Ras

Title
Suppression of Egr-1 transcription through targeting of the serum response factor by oncogenic H-Ras
Author
이영식
Keywords
Egr-1; oncogenic H-Ras; phosphoinositide 3-kinase; serum response element; serum response factor
Issue Date
2006-03
Publisher
OXFORD UNIV PRESS
Citation
EMBO JOURNAL, v. 25, No. 5, Page. 1093-1103
Abstract
The transcription factor Egr-1 functions as a key regulator in cellular growth, differentiation, and apoptosis. The loss of Egr-1 expression is closely associated with tumor development, although the molecular mechanism behind the suppression of Egr-1 is largely unknown. In this report, we show that growth factor-induced transcriptional activation of Egr-1 gene is downregulated by chronic expression of oncogenic H-Ras in NIH3T3 fibroblasts. Our results demonstrate that phosphoinositide 3-kinase (PI3K) signaling is necessary for oncogenic H-Ras-mediated reduction of Egr-1 gene expression. Aberrant activation of PI3K signaling by oncogenic Ras decreased the level of serum response factor (SRF) protein through the acceleration of proteolysis, which resulted in decreased SRF binding to the serum response element (SRE) sites within the Egr-1 promoter, leading to the suppression of Egr-1 transcription. Inhibition of PI3K signaling restored the downregulation of SRF and Egr-1 expression caused by oncogenic Ras. Our findings suggest a novel signaling mechanism by which prolonged activation of oncogenic H-Ras can trigger the loss of tumor suppressor Egr-1 through the PI3K pathway in NIH3T3 fibroblast model cell lines.
URI
https://www.embopress.org/doi/full/10.1038/sj.emboj.7600987http://repository.hanyang.ac.kr/handle/20.500.11754/107787
ISSN
0261-4189; 1460-2075
DOI
10.1038/sj.emboj.7600987
Appears in Collections:
COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > MOLECULAR AND LIFE SCIENCE(분자생명과학과) > Articles
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