Molecular and Cellular Biology, November 2000, p. 8084-8092, Vol. 20, No. 21
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
B
Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas 752351; Department of Medicine and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 104612; and Institute Curie, Paris, France3
Received 2 June 2000/Returned for modification 26 June 2000/Accepted 9 August 2000
Ral GTPases have been implicated as mediators of Ras-induced signal
transduction from observations that Ral-specific guanine nucleotide
exchange factors associate with Ras and are activated by Ras. The
cellular role of Ral family proteins is unclear, as is the contribution
that Ral may make to Ras-dependent signaling. Here we show that
expression of activated Ral in quiescent rodent fibroblasts is
sufficient to induce activation of NF-
B-dependent gene expression
and cyclin D1 transcription, two key convergence points for mitogenic
and survival signaling. The regulation of cyclin D1 transcription by
Ral is dependent on NF-
B activation and is mediated through an
NF-
B binding site in the cyclin D1 promoter. Ral activation of these
responses is likely through an as yet uncharacterized effector pathway,
as we find activation of NF-
B and the cyclin D1 promoter by Ral is
independent of association of Ral with active phospholipase D1 or
Ral-binding protein 1, two proteins proposed to mediate Ral function in cells.
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