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Proteomic analysis of phosphorylated nuclear proteins underscores novel roles for rapid actions of retinoic acid in the regulation of mRNA splicing and translation

AuthorsLaserna Mendieta, Emilio J.; Valero, M. Luz; Sanz, Libia ; Sánchez del Pino, Manuel M.; Calvete, Juan J. ; Barettino, Domingo
Issue Date25-Sep-2009
CitationEMBO conference on nuclear receptors: from molecular mechanisms to molecular medicine. (2009)
AbstractP. 162 Retinoic Acid (RA) signaling is mediated by the Retinoic Acid Receptor (RAR), belonging to the Nuclear Hormone Receptor superfamily. In addition to its classical transcriptional actions, RAR also mediates rapid transcription-independent actions (also called non-genomic), consisting in the activation of signal transduction pathways, as the phosphatidyl-inositol-3-kinase (PI3K) or the ERK MAP-kinase signaling pathways. RA-induced rapid actions play roles in different physiological contexts. As an effort towards understanding the functions of those rapid actions on signaling elicited by RA, we have identified nuclear proteins whose phosphorylation state is rapidly modified by RA treatment in neuroblastoma cells, using a proteomic approach. Our results show that RA treatment led to changes in the phosphorylation patterns in two families of proteins: (i) those related to chromatin dynamics in relation to transcriptional activation, and (ii) those related to mRNA processing and in particular mRNA splicing. We show that treatment of neuroblastoma cells with RA leads to alteration of the regulation of pre-mRNA splicing and mRNA translation, via the activation of signaling pathways. Thus, our results underscore novel functions for the non-genomic signaling elicited by RAR in the regulation of mRNA processing, as part of a cellular response orchestrated by the nuclear receptor RAR. The results shown here contribute to the idea that transcriptional and transcription-independent actions elicited by nuclear hormone receptors are integrated and converge at multiple levels in the regulation of gene expression.
DescriptionPóster original presentado EMBO conferences on nuclear receptors: from nuclear mechanisms to molecular medicine, celebrado en Croatia, 25-29 September, 2009. (P. 162)
Appears in Collections:(IBV) Comunicaciones congresos
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