Cell Growth & Differentiation, Vol 1, Issue 12 601-606, Copyright © 1990 by American Association of Cancer Research
A nuclear factor that binds to ras-responsive enhancer elements is present in human tumor cells
RD Owen and MC Ostrowski
Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710.
The ras protein can be viewed as molecular switches for undetermined signal
transduction pathways. We are interested in defining the downstream
effectors and targets associated with ras signal transduction. A nuclear
target of ras action is the conserved sequence element TGACTCT, which
functions as a ras-responsive transcriptional element (RRE). An Mr 120,000
nuclear factor present in transformed murine cells recognizes the RRE.
Mutation of the conserved RRE element to the palindromic element AGACTCT
created a binding site that is recognized with 5-fold greater affinity by
the Mr 120,000 factor. The palindromic element functions as an RRE as
determined by transient transfection assays. UV-crosslinking of nuclear
factors in human tumor cell lines to the palindromic element revealed that
an Mr 120,000 factor that recognized RREs was present in cells that contain
activated Ha- or N-ras genes, but not in human tumor cells that lack
activated ras. Expression of exogenous activated ras in a human tumor cell
line that lacks the oncogene induced the Mr 120,000 factor. The Mr 120,000
factor, which we have termed ras-responsive factor 1, is an intermediate in
the signal transduction pathway that links ras to the nucleus and may play
a role in the initiation or progression of human tumors containing an
activated ras gene.