+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



Journal of Biological Chemistry 280(46): 38365-38375



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 013182426

Download citation: RISBibTeXText

PMID: 16087680

DOI: 10.1074/jbc.m501609200


Related references

Activation of bone sialoprotein gene transcription by flavonoids is mediated through an inverted CCAAT box in ROS 17/2.8 cells. Journal of Cellular Biochemistry 86(1): 35-44, 2002

Transcription of the bone sialoprotein gene is stimulated by v-Src acting through an inverted CCAAT box. Cancer Research 59(3): 565-571, 1999

Mechanism of NFY-1 mediated regulation of bone sialoprotein gene transcription through an inverted CCAAT box. Journal of Bone & Mineral Research 15(Suppl 1): S374, 2000

Characterization of the human bone sialoprotein gene Identification of inverted TATA and CCAAT boxes in the gene promoter. Journal of Cellular Biochemistry Supplement 0(17 PART E): 162, 1993

Amelogenin stimulates bone sialoprotein (BSP) expression through fibroblast growth factor 2 response element and transforming growth factor-beta1 activation element in the promoter of the BSP gene. Journal of Periodontology 76(9): 1482-1489, 2005

CCAAT/enhancer-binding protein beta (nuclear factor for interleukin 6) transactivates the human MDR1 gene by interaction with an inverted CCAAT box in human cancer cells. Molecular Pharmacology 65(4): 906-916, 2004

Stereochemical analysis of the functional significance of the conserved inverted CCAAT and TATA elements in the rat bone sialoprotein gene promoter. Journal of Biological Chemistry 281(15): 9882-9890, 2006

Androgen receptor stimulates bone sialoprotein (BSP) gene transcription via cAMP response element and activator protein 1/glucocorticoid response elements. Journal of Cellular Biochemistry 102(1): 240-251, 2007

An inverted TATA box directs downstream transcription of the bone sialoprotein gene. Biochemical Journal 310: 33-40, 1995

The pentanucleotide ATTGG, the "inverted CCAAT," is an essential element for HLA class I gene transcription. Journal of Immunology 158(10): 4788-4796, 1997

Transforming growth factor-beta 1 regulation of bone sialoprotein gene transcription: identification of a TGF-beta activation element in the rat BSP gene promoter. Journal of Cellular Biochemistry 65(4): 501-512, 1997

Transforming growth factor beta 1-responsive element: closely associated binding sites for Usf and Ccaat-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene. Molecular and Cellular Biology 12(4): 1846-1855, 1992

Transforming growth factor beta 1 responsive element closely associated binding sites for usf and ccaat binding transcription factor nuclear factor i in the type 1 plasminogen activator inhibitor gene. Molecular & Cellular Biology 12(4): 1846-1855, 1992

Kaempferol stimulates bone sialoprotein gene transcription and new bone formation. Journal of Cellular Biochemistry 110(6): 1342-1355, 2010

Identification of a vitamin D 3 -response element that overlaps a unique inverted Tata box in the rat bone sialoprotein gene. Biochemical Journal 318(1): 219-226, 1996