HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 46, 38365-38375, November 18, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/46/38365    most recent M501609200v1 Submit a Letter to Editor 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 Su, M. Articles by Sodek, J. Search for Related Content PubMed PubMed Citation Articles by Su, M. Articles by Sodek, J. Social Bookmarking                      What's this?

Recruitment of Nuclear Factor Y to the Inverted CCAAT Element (ICE) by c-Jun and E1A Stimulates Basal Transcription of the Bone Sialoprotein Gene in Osteosarcoma Cells^*

Ming Su1, Anil K. Bansal, Roberto Mantovani, and Jaro Sodek¶

From the Canadian Institutes of Health Research Group in Matrix Dynamics, Faculty of Dentistry and ^¶Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 3E2, Canada and the Dipartimento di Scienze Biomolecolari e Biotecnologie, Università di Milano, 20143 Milano, Italy

Bone sialoprotein (BSP), a major protein in the extracellular matrix of bone, is expressed almost exclusively by bone cells and by cancer cells that have a propensity to metastasize to bone. Previous studies have shown that v-src stimulates basal transcription of bsp in osteosarcoma (ROS 17/2.8) cells by targeting the inverted CCAAT element (ICE) in the proximal promoter. To identify possible downstream effectors of Src we studied the effects of the proto-oncogene c-jun, which functions downstream of Src, on basal transcription of bsp using transient transfection assays. Increased expression of endogenous c-Jun induced by the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate and ectopic expression of c-Jun increased basal transcription of chimeric reporter constructs encompassing the proximal promoter by 1.5–3-fold in ROS 17/2.8 osteosarcoma cells, with more modest effects in a normal bone cell line, RBMC-D8. The effects of c-Jun were abrogated by mutations in the ICE box and by co-expression of dominant negative nuclear factor Y, subunit A (NF-YA). The increase in bsp transcription did not require phosphorylation of c-Jun and was not altered by trichostatin treatment or by ectopic expression of p300/CREB-binding protein (CBP) or mutated forms lacking histone acetyltransferase (HAT) activity. Similarly, ectopic expression of p300/CBP-associated factor (P/CAF), which transduces p300/CBP effects, or of HAT-defective P/CAF did not influence the c-jun effects. Surprisingly, E1A, which competes with P/CAF binding to p300/CBP, also stimulated BSP transcription through NF-Y independently of c-jun, p300/CBP, and P/CAF. Collectively, these studies show that c-Jun and E1A regulate basal transcription of bsp in osteosarcoma cells by recruiting the NF-Y transcriptional complex to the ICE box in a mechanism that is independent of p300/CBP and P/CAF HAT activities.

Received for publication, February 11, 2005 , and in revised form, July 18, 2005.

^* These studies were supported by Canadian Institutes of Health Research (CIHR) Grant MOP 37785. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: CIHR Group in Matrix Dynamics, Faculty of Dentistry, 234 FitzGerald Bldg., 150 College St., University of Toronto, Toronto, ON M5S 3E2, Canada. Tel.: 416-978-6624; Fax: 416-978-5956; E-mail: m.su{at}utoronto.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Chen, J. Gluhak-Heinrich, M. Martinez, T. Li, Y. Wu, H.-H. Chuang, L. Chen, J. Dong, I. Gay, and M. MacDougall Bone Morphogenetic Protein 2 Mediates Dentin Sialophosphoprotein Expression and Odontoblast Differentiation via NF-Y Signaling J. Biol. Chem., July 11, 2008; 283(28): 19359 - 19370. [Abstract] [Full Text] [PDF]

				K. Toualbi-Abed, F. Daniel, M. C. Guller, A. Legrand, J.-L. Mauriz, A. Mauviel, and D. Bernuau Jun D cooperates with p65 to activate the proximal {kappa}B site of the cyclin D1 promoter: role of PI3K/PDK-1 Carcinogenesis, March 1, 2008; 29(3): 536 - 543. [Abstract] [Full Text] [PDF]

				M. Su, D. Lee, B. Ganss, and J. Sodek Stereochemical Analysis of the Functional Significance of the Conserved Inverted CCAAT and TATA Elements in the Rat Bone Sialoprotein Gene Promoter J. Biol. Chem., April 14, 2006; 281(15): 9882 - 9890. [Abstract] [Full Text] [PDF]