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Titolo:
INTERACTION OF HIV-1 TAT PROTEIN WITH HEPARIN - ROLE OF THE BACKBONE STRUCTURE, SULFATION, AND SIZE
Autore:
RUSNATI M; COLTRINI D; ORESTE P; ZOPPETTI G; ALBINI A; NOONAN D; DIFAGAGNA FD; GIACCA M; PRESTA M;
Indirizzi:
UNIV BRESCIA,SCH MED,DEPT BIOMED SCI & BIOTECHNOL,CHAIR GEN PATHOL & IMMUNOL,VIA VALSABBINA 19 I-25123 BRESCIA ITALY UNIV BRESCIA,SCH MED,DEPT BIOMED SCI & BIOTECHNOL,CHAIR GEN PATHOL & IMMUNOL I-25123 BRESCIA ITALY GLYCOSAMINOGLYCAN CONSULTANTS I-20100 MILAN ITALY IST NAZL RIC CANC I-16132 GENOA ITALY INT CTR GENET ENGN & BIOTECHNOL I-34012 TRIESTE ITALY
Titolo Testata:
The Journal of biological chemistry
fascicolo: 17, volume: 272, anno: 1997,
pagine: 11313 - 11320
SICI:
0021-9258(1997)272:17<11313:IOHTPW>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; FIBROBLAST GROWTH-FACTOR; TRANS-ACTIVATOR GENE; DEXTRAN SULFATE; BASIC DOMAIN; BIOLOGICAL PROPERTIES; ENDOTHELIAL-CELLS; HTLV-III; TYPE-1; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
80
Recensione:
Indirizzi per estratti:
Citazione:
M. Rusnati et al., "INTERACTION OF HIV-1 TAT PROTEIN WITH HEPARIN - ROLE OF THE BACKBONE STRUCTURE, SULFATION, AND SIZE", The Journal of biological chemistry, 272(17), 1997, pp. 11313-11320

Abstract

Human immunodeficiency virus type 1 (HIV-1) Tat protein is released from infected cells. Extracellular Tat enters the cell where it stimulates the transcriptional activity of HIV-long terminal repeat (LTR) andof endogenous genes. Heparin modulates the angiogenic (Albini, A., Benelli, R., Presta, M., Rusnati, M., Ziche, M., Rubartelli, A., Paglialunga, G., Bussolino, F., and Noonan, D. (1996) Oncogene 12, 289-297) and transcriptional (Mann, D. A., and Frankel, A. D. (1991) EMBO J. 10;1733-1739) activity of extracellular Tat. Here we demonstrate that heparin binds specifically to recombinant HIV-1 Tat produced as glutathione S-transferase (GST) fusion protein add immobilized on glutathione-agarose beads. Heparin and heparan sulfate (HS), but not dermatan sulfate, chondroitin sulfates A and C, hyaluronic acid, and K5 polysaccharide, competed with H-3-labeled heparin for binding to immobilized GST-Tat and inhibited HIV-LTR transactivation induced by extracellular GST-Tat. Selective 2-0-, 6 O-, total-O-desulfation, or N-desulfation/N-acetylation dramatically reduced the capacity of heparin to bind GST-Tat. Totally-O-desulfated and 2-O-desulfated heparins also showed a reduced capacity to inhibit the transactivating activity of GST-Tat. Very low molecular weight heparins showed a significant decrease in their capacity to bind GST-Tat and to inhibit its LTR transactivating activitywhen compared with conventional 13.6-kDa heparin. However, when 3.0-kDa heparin was affinity chromatographed on immobilized GST-Tat to isolate binding and non-binding subfrac tions, the Tat-bound fraction was greater than or equal to 1,000 times more potent than the unbound fraction in inhibiting the transactivating activity of GST-Tat. The results demonstrate that Tat interacts in a size-dependent manner with heparin/HS and that high affinity Tat heparin interaction requires at leastsome 2-O, 6-O-, and N-positions to be sulfated. The Tat binding activity of the glycosaminoglycans tested correlates with their capacity toaffect the transactivating activity of extracellular Tat, indicating the possibility to design specific heparin/HS-like structures with Tat-antagonist activity.

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Documento generato il 30/11/20 alle ore 16:32:17