Cargando…

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

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 fibroblas...

Descripción completa

Detalles Bibliográficos
Autores principales: Castellano, Esther, Guerrero, Carmen, Núñez, Alejandro, De Las Rivas, Javier, Santos, Eugenio
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091317/
https://www.ncbi.nlm.nih.gov/pubmed/19895680
http://dx.doi.org/10.1186/gb-2009-10-11-r123
_version_ 1782203239640334336
author Castellano, Esther
Guerrero, Carmen
Núñez, Alejandro
De Las Rivas, Javier
Santos, Eugenio
author_facet Castellano, Esther
Guerrero, Carmen
Núñez, Alejandro
De Las Rivas, Javier
Santos, Eugenio
author_sort Castellano, Esther
collection PubMed
description 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 post-starvation 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 H-Ras and N-Ras during those processes.
format Text
id pubmed-3091317
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-30913172011-05-10 Serum-dependent transcriptional networks identify distinct functional roles for H-Ras and N-Ras during initial stages of the cell cycle Castellano, Esther Guerrero, Carmen Núñez, Alejandro De Las Rivas, Javier Santos, Eugenio Genome Biol Research 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 post-starvation 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 H-Ras and N-Ras during those processes. BioMed Central 2009 2009-11-06 /pmc/articles/PMC3091317/ /pubmed/19895680 http://dx.doi.org/10.1186/gb-2009-10-11-r123 Text en Copyright ©2009 Castellano et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Castellano, Esther
Guerrero, Carmen
Núñez, Alejandro
De Las Rivas, Javier
Santos, Eugenio
Serum-dependent transcriptional networks identify distinct functional roles for H-Ras and N-Ras during initial stages of the cell cycle
title Serum-dependent transcriptional networks identify distinct functional roles for H-Ras and N-Ras during initial stages of the cell cycle
title_full Serum-dependent transcriptional networks identify distinct functional roles for H-Ras and N-Ras during initial stages of the cell cycle
title_fullStr Serum-dependent transcriptional networks identify distinct functional roles for H-Ras and N-Ras during initial stages of the cell cycle
title_full_unstemmed Serum-dependent transcriptional networks identify distinct functional roles for H-Ras and N-Ras during initial stages of the cell cycle
title_short Serum-dependent transcriptional networks identify distinct functional roles for H-Ras and N-Ras during initial stages of the cell cycle
title_sort serum-dependent transcriptional networks identify distinct functional roles for h-ras and n-ras during initial stages of the cell cycle
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091317/
https://www.ncbi.nlm.nih.gov/pubmed/19895680
http://dx.doi.org/10.1186/gb-2009-10-11-r123
work_keys_str_mv AT castellanoesther serumdependenttranscriptionalnetworksidentifydistinctfunctionalrolesforhrasandnrasduringinitialstagesofthecellcycle
AT guerrerocarmen serumdependenttranscriptionalnetworksidentifydistinctfunctionalrolesforhrasandnrasduringinitialstagesofthecellcycle
AT nunezalejandro serumdependenttranscriptionalnetworksidentifydistinctfunctionalrolesforhrasandnrasduringinitialstagesofthecellcycle
AT delasrivasjavier serumdependenttranscriptionalnetworksidentifydistinctfunctionalrolesforhrasandnrasduringinitialstagesofthecellcycle
AT santoseugenio serumdependenttranscriptionalnetworksidentifydistinctfunctionalrolesforhrasandnrasduringinitialstagesofthecellcycle