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Title

Cold-Inducible RNA-Binding Protein Bypasses Replicative Senescence in Primary Cells through Extracellular Signal-Regulated Kinase 1 and 2 Activation

AuthorsArtero-Castro, Ana; Callejas, Francisco B.; Castellvi, Josep; Kondoh, Hiroshi; Carnero, Amancio CSIC ORCID; Fernández-Marcos, Pablo J.; Serrano, Manuel; Ramón y Cajal, Santiago; Lleonart, Matilde E.
KeywordsCell anging
Embryo
Mammalian
Enzyme activation
Fibroblasts
Mice
Mitogen-activated protein Kinase 1
Neoplasms
Phosphorylation
Protein biosynthesis
RNA-binding proteins
Issue Date21-Jan-2009
PublisherAmerican Society for Microbiology
CitationMolecular and Cellular Biology 29(7): 1855-1868 (2009)
AbstractEmbryonic stem cells are immortalized cells whose proliferation rate is comparable to that of carcinogenic cells. To study the expression of embryonic stem cell genes in primary cells, genetic screening was performed by infecting mouse embryonic fibroblasts (MEFs) with a cDNA library from embryonic stem cells. Cold-inducible RNA-binding protein (CIRP) was identified due to its ability to bypass replicative senescence in primary cells. CIRP enhanced extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, and treatment with an MEK inhibitor decreased the proliferation caused by CIRP. In contrast to CIRP upregulation, CIRP downregulation decreased cell proliferation and resulted in inhibition of phosphorylated ERK1/2 inhibition. This is the first evidence that ERK1/2 activation, through the same mechanism as that described for a Val12 mutant K-ras to induce premature senescence, is able to bypass senescence in the absence of p16INK4a, p21WAF1, and p19ARF upregulation. Moreover, these results show that CIRP functions by stimulating general protein synthesis with the involvement of the S6 and 4E-BP1 proteins. The overall effect is an increase in kinase activity of the cyclin D1-CDK4 complex, which is in accordance with the proliferative capacity of CIRP MEFs. Interestingly, CIRP mRNA and protein were upregulated in a subgroup of cancer patients, a finding that may be of relevance for cancer research.
Description14 páginas, 9 figuras, 1 tabla.
Publisher version (URL)http://dx.doi.org/ 10.1128/MCB.01386-08
URIhttp://hdl.handle.net/10261/38829
DOIhttp://dx.doi.org/10.1128/MCB.01386-08
ISSN1098-5549
E-ISSN0270-7306
Appears in Collections:(IBIS) Artículos
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