TRANSFORMING-GROWTH-FACTOR-BETA STIMULATES THE HUMAN-IMMUNODEFICIENCY-VIRUS-1 ENHANCER AND REQUIRES NF-KAPPA-B ACTIVITY

Citation
Jm. Li et al., TRANSFORMING-GROWTH-FACTOR-BETA STIMULATES THE HUMAN-IMMUNODEFICIENCY-VIRUS-1 ENHANCER AND REQUIRES NF-KAPPA-B ACTIVITY, Molecular and cellular biology, 18(1), 1998, pp. 110-121
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,"Cell Biology
Journal title
ISSN journal
0270-7306
Volume
18
Issue
1
Year of publication
1998
Pages
110 - 121
Database
ISI
SICI code
0270-7306(1998)18:1<110:TSTH>2.0.ZU;2-B
Abstract
Transforming growth factor beta (TGF-beta) is the prototype of a large superfamily of signaling molecules involved in the regulation of cell growth and differentiation. In certain patients infected with human i mmunodeficiency virus type 1 (HIV-1), increased levels of TGF-beta pro moted the production of virus and also impaired the host immune system . In an effort to understand the signaling events linking TGF-beta act ion and HIV production, we show here that TGF-beta can stimulate trans cription from the HIV-1 long terminal repeat (LTR) promoter through NF -kappa B binding sites in both HaCaT and 300.19 pre-B cells. When intr oduced into a minimal promoter, NF-kappa B binding sites supported nea rly 30-fold activation from the luciferase reporter upon TGF-beta trea tment, Electrophoretic mobility shift assay indicated that a major fac tor binding to the NF-KB site is the p50-p65 heterodimeric NF-kappa B in HaCaT cells. Coexpression of Gal4-p65 chimeric proteins supported T GF-beta ligand-dependent gene expression from a luciferase reporter ge ne driven by Gal4 DNA binding sites, NF-kappa B activity present in Ha CaT cells was not affected by TGF-beta treatment as judged by the unch anged DNA binding activity and concentrations of p50 and p65 proteins, Consistently, steady-state levels of I kappa B gamma and I kappa B be ta proteins were not changed by TGF-beta treatment, Our results demons trate that TGF-beta is able to stimulate transcription from the HIV-1 LTR promoter by activating NF-kappa B through a mechanism distinct fro m the classic NF-kappa B activation mechanism involving the degradatio n of I kappa B proteins.