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Type: Journal article
Title: DNA binding-independent transcriptional activation of the vascular endothelial growth factor gene (VEGF) by the Myb oncoprotein
Author: Lutwyche, J.
Keough, R.
Hunter, J.
Coles, L.
Gonda, T.
Citation: Biochemical and Biophysical Research Communications, 2006; 344(4):1300-1307
Publisher: Academic Press Inc
Issue Date: 2006
ISSN: 0006-291X
Organisation: Centre for the Molecular Genetics of Development
Statement of
Jodi K. Lutwyche, Rebecca A. Keough, Julie Hunter, Leeanne S. Coles and Thomas J. Gonda
Abstract: Myb is a key transcription factor that can regulate proliferation, differentiation, and apoptosis, predominantly in the haemopoietic system. Abnormal expression of Myb is associated with a number of cancers, both haemopoietic and non-haemopoietic. In order to better understand the role of Myb in normal and tumorigenic processes, we undertook a cDNA array screen to identify genes that are regulated by this factor. In this way, we identified the gene encoding vascular endothelial growth factor (VEGF) as being potentially regulated by the Myb oncoprotein in myeloid cells. To determine whether this was a direct effect on VEGF gene transcription, we examined the activity of the murine VEGF promoter in the presence of either wild-type (WT) or mutant forms of Myb. It was found that WT Myb was able to activate the VEGF promoter and that a minimal promoter region of 120 bp was sufficient to confer Myb responsiveness. Surprisingly, activation of the VEGF promoter was independent of DNA binding by Myb. This was shown by the use of DNA binding-defective Myb mutants and by mutagenesis of a potential Myb-binding site in the minimal promoter. Mutation of Sp1 sites within this region abolished Myb-mediated regulation of a reporter construct, suggesting that Myb DNA binding-independent activation of VEGF expression occurs via these Sp1 binding elements. Regulation of VEGF production by Myb has implications for the potential role of Myb in myeloid leukaemias and in solid tumours where VEGF may be functioning as an autocrine growth factor.
Keywords: Myb; VEGF promoter; Transactivation; Angiogenesis; Autocrine; DNA binding
Rights: © 2006 Elsevier Inc. All rights reserved.
RMID: 0020060556
DOI: 10.1016/j.bbrc.2006.04.045
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Appears in Collections:Centre for the Molecular Genetics of Development publications
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