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


  • eng

Conference Location

  • United States