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Serum-dependent transcriptional networks identify distinct functional roles for H-Ras and N-Ras during initial stages of the cell cycle

AutorCastellano, Esther; Guerrero Arroyo, María del Carmen ; Núñez, Alejandro; De Las Rivas, Javier ; Santos de Dios, Eugenio
Fecha de publicaciónnov-2009
EditorBioMed Central
CitaciónGenome Biology 10: R123 (2009)
Resumen[Background]: Using oligonucleotide microarrays, we compared transcriptional profiles corresponding to the initial cell cycle stages of mouse fibroblasts lacking the small GTPases H-Ras and/or N-Ras with those of matching, wild-type controls.
[Results]: Serum-starved wild-type and knockout ras fibroblasts had very similar transcriptional profiles, indicating that H-Ras and N-Ras do not significantly control transcriptional responses to serum deprivation stress. In contrast, genomic disruption of H-ras or N-ras, individually or in combination, determined specific differential gene expression profiles in response to poststarvation stimulation with serum for 1 hour (G0/G1 transition) or 8 hours (mid-G1 progression). The absence of N-Ras caused significantly higher changes than the absence of H-Ras in the wave of transcriptional activation linked to G0/G1 transition. In contrast, the absence of H-Ras affected the profile of the transcriptional wave detected during G1 progression more strongly than did the absence of N-Ras. H-Ras was predominantly functionally associated with growth and proliferation, whereas N-Ras had a closer link to the regulation of development, the cell cycle, immunomodulation and apoptosis. Mechanistic analysis indicated that extracellular signal-regulated kinase (ERK)-dependent activation of signal transducer and activator of transcription 1 (Stat1) mediates the regulatory effect of N-Ras on defense and immunity, whereas the pro-apoptotic effects of N-Ras are mediated through ERK and p38 mitogen-activated protein kinase signaling.
[Conclusions]: Our observations confirm the notion of an absolute requirement for different peaks of Ras activity during the initial stages of the cell cycle and document the functional specificity of HRas and N-Ras during those processes.
Descripción24 pages, 9 figures, 2 tables.-- This is an open access article distributed under the terms of the Creative Commons Attribution License.
Versión del editorhttp://dx.doi.org/10.1186/gb-2009-10-11-r123
URIhttp://hdl.handle.net/10261/20162
DOI10.1186/gb-2009-10-11-r123
ISSN1465-6906
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