Abstract
Transcriptional and functional analysis reveals that the H-Ras and N-Ras isoforms have different roles in the initial phases of the mouse cell cycle
Highlights
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
Analysis of serum-dependent, transcriptional profiles in wild-type and ras knockout fibroblasts To ascertain whether or not the different members of the Ras family control the expression of specific gene sets in response to the absence or presence of serum in cell cultures, we used commercial oligonucleotide microarrays to compare the genomic expression profile of serum-starved or serumtreated, WT, immortalized fibroblasts with those of treated fibroblasts derived from knockout mice harboring single- or double-null mutations for the H-ras and N-ras loci (H-ras-/, N-ras-/, H-ras-/-/N-ras-/-)
The results from microarray hybridizations corresponding to cell cultures subjected to serum starvation for 24 hours were instrumental to characterize the transcriptional profile of non-proliferating, off-cycle fibroblasts arrested in G0 because of the absence of growth factors caused by serum withdrawal from the cultures
Summary
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. The mammalian H-Ras, N-Ras and K-Ras proteins are highly related small GTPases functioning as critical components of cellular signaling pathways controlling proliferation, differentiation or survival They act as molecular switches cycling between inactive (GDP-bound) and active (GTP-bound) states in a process modulated under physiological conditions by a variety of specific regulatory proteins, including GAPs (GTPase activating proteins) and GEFs (guanine nucleotide exchange factors) [1,2,3]. Our recent characterization of the transcriptional networks of actively growing cultures of fibroblast cells harboring single or double null mutations in the H-ras and N-ras loci clearly supported the notion of different functions for H-Ras and NRas by documenting a significant involvement of N-Ras in immunomodulation/defense and apoptotic responses [35]
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