Human thioredoxin/adult T cell leukemia-derived factor activates the enhancer binding protein of human immunodeficiency virus type 1 by thiol redox control mechanism

Publisher Website
Google Scholar
Abstract
Transcription from the human immunodeficiency virus type 1 (HIV-1) provirus is activated by a cellular factor, NFκB, recognizing the tandemly repeated 10-base-pair sequences, termed the κB sequence, present in the enhancer region within the viral long terminal repeat (LTR). Using electrophoretic mobility shift assay (EMSA), which demonstrates specific DNA-protein interaction in vitro, we could demonstrate that reducto-oxidatlve modulation of NFκB dramatically changes its DNA binding activity and that a cellular physiological reducing catalyst, thioredoxin (TRX) also known as adult T cell leukemia derived factor (ADF), fully restored the DNA-binding activity of the oxidized NFκB. We also observed that purified TRX/ADF protein could augment gene expression from HIV LTR as demonstrated by transient chloramphenicol acetyltransferase (CAT) assay. These observations confirmed the previous notion that ADF might be an inducing factor of cellular interleukin-2 receptor a subunit (IL-2Rα) through the κB sequence that is a common central cis-regulatory element in both IL-2Rα and HIV gene expression. These observations indicate that reducto-oxidative regulation (or redox regulation) of a cysteine residue(s) on the NFκB molecule might play an important role in its specific DNA interaction and that it might provide a clue to the understanding of a pathway of cellular signal transductlon to NFκB that is independent from the known pathways Involving protein phosphorylation.

This publication has 0 references indexed in Scilit: