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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.

Ral GTPases Contribute to Regulation of Cyclin D1 through Activation of NF-kappa B

Dale O. Henry,1 Serge A. Moskalenko,1 Kiran J. Kaur,1 Maofu Fu,2 Richard G. Pestell,2 Jacques H. Camonis,3 and Michael A. White1,*

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-kappa 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-kappa B activation and is mediated through an NF-kappa 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-kappa 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.

* Corresponding author. Mailing address: Department of Cell Biology, UT Southwestern Medical Center, Dallas, TX 75235. Phone: (214) 648-2861. Fax: (214) 648-8694. E-mail: white08{at}utsw.swmed.edu.

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.


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