Cell Growth & Differentiation, Vol 6, Issue 5 549-556, Copyright © 1995 by American Association of Cancer Research

ARTICLES

v-Raf activates transcription of growth-responsive promoters via GC-rich sequences that bind the transcription factor Sp1

RJ Miltenberger, PJ Farnham, DE Smith, JM Stommel and MM Cornwell
McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison 53706, USA.

The serine/threonine kinase, Raf-1, is a component of intracellular signaling pathways that control responses to extracellular stimuli. Previously, we have shown that serum-induced transcription from the murine rep-3b and human mdr1 promoters is Raf-dependent and that the activated Raf kinase, v-Raf, induces transcription of mdr1 via a GC-rich element. We now demonstrate that GC-rich sequences in the rep-3b promoter are both necessary and sufficient for induction by v-Raf. The GC-rich, v-Raf-responsive elements of rep-3b and mdr1 bind the general transcription factor Sp1 in electromobility shift assays. Mutation of a minimal GC-rich element abolished inducibility by v-Raf and eliminated binding by the transcription factor Sp1. However, Sp1 binding activity following serum stimulation of quiescent NIH 3T3 cells was unchanged, suggesting that mitogenic signals may stimulate the transactivation potential of prebound Sp1.

This article has been cited by other articles:

				G. Wang, A. B. Leiter, E. W. Englander, and G. H. Greeley Jr. Insulin-Like Growth Factor I Increases Rat Peptide YY Promoter Activity through Sp1 Binding Sites Endocrinology, February 1, 2004; 145(2): 659 - 666. [Abstract] [Full Text] [PDF]

				K. W. Scotto and R. A. Johnson Transcription of MDR1: A Therapeutic Target Mol. Interv., June 1, 2001; 1(2): 117 - 125. [Abstract] [Full Text] [PDF]

				S. Chupreta, M. Du, A. Todisco, and J. L. Merchant EGF stimulates gastrin promoter through activation of Sp1 kinase activity Am J Physiol Cell Physiol, April 1, 2000; 278(4): C697 - C708. [Abstract] [Full Text] [PDF]

				Z. Hu, S. Jin, and K. W. Scotto Transcriptional Activation of the MDR1 Gene by UV Irradiation. ROLE OF NF-Y AND Sp1 J. Biol. Chem., January 28, 2000; 275(4): 2979 - 2985. [Abstract] [Full Text] [PDF]

				C. J. Fry and P. J. Farnham Context-dependent Transcriptional Regulation J. Biol. Chem., October 15, 1999; 274(42): 29583 - 29586. [Full Text] [PDF]

				C. McCoy, S. B. McGee, and M. M. Cornwell The Wilms' Tumor Suppressor, WT1, Inhibits 12-O-Tetradecanoylphorbol-13-acetate Activation of the Multidrug Resistance-1 Promoter Cell Growth Differ., June 1, 1999; 10(6): 377 - 386. [Abstract] [Full Text]

				A. R. Black, D. Jensen, S.-Y. Lin, and J. C. Azizkhan Growth/Cell Cycle Regulation of Sp1 Phosphorylation J. Biol. Chem., January 15, 1999; 274(3): 1207 - 1215. [Abstract] [Full Text] [PDF]

				R. Duan, W. Porter, and S. Safe Estrogen-Induced c-fos Protooncogene Expression in MCF-7 Human Breast Cancer Cells: Role of Estrogen Receptor Sp1 Complex Formation Endocrinology, April 1, 1998; 139(4): 1981 - 1990. [Abstract] [Full Text] [PDF]

				H. T. Cohen, S. A. Bossone, G. Zhu, G. A. McDonald, and V. P. Sukhatme Sp1 Is a Critical Regulator of the Wilms' tumor-1 Gene J. Biol. Chem., January 31, 1997; 272(5): 2901 - 2913. [Abstract] [Full Text] [PDF]

				A. Liu, M. S. Prenger, D. D. Norton, L. Mei, J. W. Kusiak, and G. Bai Nerve Growth Factor Uses Ras/ERK and Phosphatidylinositol 3-Kinase Cascades to Up-regulate the N-Methyl-D-aspartate Receptor 1 Promoter J. Biol. Chem., November 21, 2001; 276(48): 45372 - 45379. [Abstract] [Full Text] [PDF]