Open AccessTransforming Growth Factor β Stimulates the Human Immunodeficiency Virus 1 Enhancer and Requires NF-κB Activity
Author(s) -
Jianming Li,
Xinghai Shen,
Patrick Pei-chih Hu,
Xiaofan Wang
Publication year - 1998
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.18.1.110
Subject(s) - biology , enhancer , hacat , transcription factor , luciferase , transforming growth factor , reporter gene , microbiology and biotechnology , hiv long terminal repeat , electrophoretic mobility shift assay , jurkat cells , promoter , nfkb1 , transcription (linguistics) , binding site , long terminal repeat , gene expression , gene , cell culture , transfection , immune system , genetics , t cell , linguistics , philosophy
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.