Transforming growth factor beta stimulates the human immunodeficiency virus 1 enhancer and requires NF-kappaB activity.
Journal Article (Journal Article)
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 immunodeficiency virus type 1 (HIV-1), increased levels of TGF-beta promoted the production of virus and also impaired the host immune system. In an effort to understand the signaling events linking TGF-beta action and HIV production, we show here that TGF-beta can stimulate transcription from the HIV-1 long terminal repeat (LTR) promoter through NF-kappaB binding sites in both HaCaT and 300.19 pre-B cells. When introduced into a minimal promoter, NF-kappaB binding sites supported nearly 30-fold activation from the luciferase reporter upon TGF-beta treatment. Electrophoretic mobility shift assay indicated that a major factor binding to the NF-kappaB site is the p50-p65 heterodimeric NF-kappaB in HaCaT cells. Coexpression of Gal4-p65 chimeric proteins supported TGF-beta ligand-dependent gene expression from a luciferase reporter gene driven by Gal4 DNA binding sites. NF-kappaB activity present in HaCaT cells was not affected by TGF-beta treatment as judged by the unchanged DNA binding activity and concentrations of p50 and p65 proteins. Consistently, steady-state levels of IkappaB alpha and IkappaB beta proteins were not changed by TGF-beta treatment. Our results demonstrate that TGF-beta is able to stimulate transcription from the HIV-1 LTR promoter by activating NF-kappaB through a mechanism distinct from the classic NF-kappaB activation mechanism involving the degradation of IkappaB proteins.
Full Text
Duke Authors
Cited Authors
- Li, JM; Shen, X; Hu, PP; Wang, XF
Published Date
- January 1998
Published In
Volume / Issue
- 18 / 1
Start / End Page
- 110 - 121
PubMed ID
- 9418859
Pubmed Central ID
- PMC121461
International Standard Serial Number (ISSN)
- 0270-7306
Digital Object Identifier (DOI)
- 10.1128/MCB.18.1.110
Language
- eng
Conference Location
- United States