Oncogene activation of HIV-LTR-driven expression via the NF-kappa B binding sites.
The Raf-1 proto-oncogene product is a highly regulated serine/threonine kinase that functions in signal transduction downstream from growth factor receptors and upstream from nuclear proto-oncogene products. Using a transient cotransfection assay we have found that activated Raf-1 activates expression from the HIV-LTR. Analysis of a series of 5' deletion and point mutations revealed the NF-kappa B motifs as the Raf-responsive element in the HIV-LTR. Moreover, Raf-BXB activated expression from heterologous promoters driven by the HIV NF-kappa B binding sites. In addition to Raf, we show that v-Src, v-H-Ras and v-Mos activate HIV-LTR expression through the NF-kappa B binding sites and v-H-Ras-induced HIV-LTR expression is mediated by Raf-1. These findings may have implications for the involvement of the cellular homologues of these oncogenes in the switch from latent to productive infection by HIV in response to T-cell activation.
Bruder
J T
JT
Viral Pathology Section, NCI-Frederick Cancer Research and Development Center, MD 21702-1201.
Heidecker
G
G
Tan
T H
TH
Weske
J C
JC
Derse
D
D
Rapp
U R
UR
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D015967:Gene Expression Regulation, Viral; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000378:metabolism*; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019908:Proto-Oncogene Proteins c-raf; D015533:Transcriptional Activation
D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D019908:Proto-Oncogene Proteins c-raf