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


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Article Info

DATE

2009-11-06

AUTHORS

Esther Castellano, Carmen Guerrero, Alejandro Núñez, Javier De Las Rivas, Eugenio Santos

ABSTRACT

BackgroundUsing 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.ResultsSerum-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.ConclusionsOur 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. More... »

PAGES

r123

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/gb-2009-10-11-r123

    DOI

    http://dx.doi.org/10.1186/gb-2009-10-11-r123

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/19895680


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    37 schema:description BackgroundUsing 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.ResultsSerum-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.ConclusionsOur 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.
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    44 ERK
    45 G0/G1 transition
    46 G1 progression
    47 G1 transition
    48 H-Ras
    49 N-ras
    50 RA activity
    51 RA fibroblasts
    52 ResultsSerum
    53 absence
    54 absolute requirement
    55 activation
    56 activator
    57 activity
    58 analysis
    59 apoptosis
    60 cell cycle
    61 cell cycle stage
    62 changes
    63 close link
    64 combination
    65 contrast
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    70 dependent activation
    71 deprivation stress
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    77 documents
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    80 extracellular signal-regulated kinase
    81 fibroblasts
    82 functional role
    83 functional specificity
    84 gene expression profiles
    85 genomic disruption
    86 growth
    87 higher changes
    88 hours
    89 immunity
    90 immunomodulation
    91 initial stage
    92 kinase
    93 link
    94 matching
    95 mechanistic analysis
    96 microarray
    97 mitogen-activated protein kinase
    98 mouse fibroblasts
    99 network
    100 notion
    101 observations
    102 oligonucleotide microarrays
    103 p38 mitogen-activated protein kinase
    104 peak
    105 pro-apoptotic effects
    106 process
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    108 progression
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    110 protein kinase
    111 regulation
    112 regulation of development
    113 regulatory effects
    114 requirements
    115 response
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    117 serum
    118 serum deprivation stress
    119 signal transducer
    120 signal-regulated kinase
    121 similar transcriptional profiles
    122 small GTPases H-Ras
    123 specificity
    124 stage
    125 stimulation
    126 stress
    127 transcription 1
    128 transcriptional activation
    129 transcriptional networks
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    131 transcriptional response
    132 transcriptional waves
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