Transcriptional networks of knockout cell lines identify functional specificities of H-Ras and N-Ras: significant involvement of N-Ras in biotic and ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-08-07

AUTHORS

E Castellano, J De Las Rivas, C Guerrero, E Santos

ABSTRACT

We characterized differential gene expression profiles of fibroblast cell lines harboring single or double-homozygous null mutations in H-ras and N-ras. Whereas the expression level of the individual H-, N- and K-ras genes appeared unaffected by the presence or absence of the other ras loci, significant differences were observed between the expression profiles of cells missing N-ras and/or H-ras. Absence of N-ras produced much stronger effects than absence of H-ras over the profile of the cellular transcriptome. N-ras−/− and H-ras−/− fibroblasts displayed rather antagonistic expression profiles and the transcriptome of H-ras−/− cells was significantly closer to that of wild-type fibroblasts than to that of N-ras−/− cells. Classifying all differentially expressed genes into functional categories suggested specific roles for H-Ras and N-Ras. It was particularly striking in N-ras−/− cells the upregulation of a remarkable number of immunity-related genes, as well as of several loci involved in apoptosis. Reverse-phase protein array assays demonstrated in the same N-ras−/− cells the overexpression and nuclear migration of tyrosine phosphorylated signal transducer and activator of transcription 1 (Stat1) which was concomitant with transcriptional activation mediated by interferon-stimulated response elements. Significantly enhanced numbers of apoptotic cells were also detected in cultures of N-ras−/− cells. Our data support the notion that different Ras isoforms play functionally distinct cellular roles and indicate that N-Ras is significantly involved in immune modulation/host defense and apoptotic responses More... »

PAGES

917-933

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1209845

DOI

http://dx.doi.org/10.1038/sj.onc.1209845

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1037231432

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16909116


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