This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Basheeruddin, K. Articles by Mazzone, T. Search for Related Content PubMed PubMed Citation Articles by Basheeruddin, K. Articles by Mazzone, T.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1248-1254.)
© 1995 American Heart Association, Inc.

Articles

Platelet-Derived Growth Factor Enhances Sp1 Binding to the LDL Receptor Gene

Khaja Basheeruddin; Xiaoli Li; Carol Rechtoris; Theodore Mazzone

From the Departments of Medicine and Biochemistry, Rush Medical College, Chicago, Ill.

Correspondence to Dr Theodore Mazzone, Rush Medical College, 1653 W Congress Pkwy, Chicago, IL 60612.

Abstract We have previously demonstrated that growth activation of quiescent cells enhances LDL receptor gene transcription and that the proximal 5' flanking region of the LDL receptor gene could transduce a platelet-derived growth factor (PDGF) response. This portion of the LDL receptor gene encompasses a previously characterized sterol response element and an adjacent Sp1 binding site. By use of mobility shift analyses we show that PDGF activation of quiescent cells enhances binding of Sp1 to the LDL receptor gene. Transfection analyses indicated that the Sp1 site, but not the sterol response element binding protein site, could confer PDGF responsiveness to a heterologous promoter in quiescent cells. Furthermore, cotransfection of an LDL receptor reporter gene (containing -141 to +35 bp of the LDL receptor gene promoter) along with an expression construct coding for high-level constitutive expression of an Sp1 cDNA led to marked enhancement in expression of the LDL receptor reporter gene in quiescent cells. Increased Sp1 binding due to PDGF could be due to enhanced production of Sp1; alternatively, posttranslational activation of binding could be involved. Western blot analysis showed no difference in Sp1 abundance in quiescent cells versus PDGF-stimulated cells, suggesting a posttranslational mechanism for activation of Sp1 binding by growth induction. Our data demonstrate that PDGF stimulation of quiescent cells leads to enhanced Sp1 binding to the LDL receptor gene. This enhanced binding could participate in PDGF induction of LDL receptor gene transcription.

Key Words: transcription factors • LDL receptor gene • cell growth

This article has been cited by other articles:

				J. Kotzka, D. Müller-Wieland, G. Roth, L. Kremer, M. Munck, S. Schürmann, B. Knebel, and W. Krone Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade J. Lipid Res., January 1, 2000; 41(1): 99 - 108. [Abstract] [Full Text]

				D. P. Hajjar and M. E. Haberland Lipoprotein Trafficking in Vascular Cells. MOLECULAR TROJAN HORSES AND CELLULAR SABOTEURS J. Biol. Chem., September 12, 1997; 272(37): 22975 - 22978. [Full Text] [PDF]

				K. D. Mehta, R. Chang, J. Underwood, J. Wise, and A. Kumar Identification of a Novel cis-Acting Element Participating in Maximal Induction of the Human Low Density Lipoprotein Receptor Gene Transcription in Response to Low Cellular Cholesterol Levels J. Biol. Chem., December 27, 1996; 271(52): 33616 - 33622. [Abstract] [Full Text] [PDF]