Ral GTPases contribute to regulation of cyclin D1 through activation of NF-kappaB.
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-kappaB-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-kappaB activation and is mediated through an NF-kappaB 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-kappaB 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.
Henry
D O
DO
Department of Cell Biology, UT Southwestern Medical Center, Dallas, Texas 75235, USA.
Moskalenko
S A
SA
Kaur
K J
KJ
Fu
M
M
Pestell
R G
RG
Camonis
J H
JH
White
M A
MA
D016475:3T3 Cells; D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000378:metabolism; D002470:Cell Survival; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D020690:GTPase-Activating Proteins; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D008156:Luciferases / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D050857:Synaptotagmins; D014158:Transcription, Genetic; D014162:Transfection; D020725:ral GTP-Binding Proteins / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D005656:Fungal Proteins; D020690:GTPase-Activating Proteins; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; C490620:Ralbp1 protein, mouse; C094755:Ralbp1 protein, rat; D050857:Synaptotagmins; D019938:Cyclin D1; D049452:Green Fluorescent Proteins; D008156:Luciferases; D010739:Phospholipase D; C106801:phospholipase D1; D020725:ral GTP-Binding Proteins