2024-03-29T08:45:21Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/319612021-12-27T16:06:32Zcom_10261_109com_10261_1col_10261_362
Proteomic analysis of phosphorylated nuclear proteins underscores novel roles for rapid actions of retinoic acid in the regulation of mRNA splicing and translation
Laserna Mendieta, Emilio J.
Valero, María Luz
Sanz, Libia
Sánchez del Pino, Manuel M.
Calvete, Juan J.
Barettino, Domingo
Retinoic Acid
RAR
RA
nuclear hormone receptors
neuroblastoma
PI3K
nongenomic actions
transcription-independent actions
splicing
Alternative splicing
translation
phosphorylation
16 pages, 8 figures, 6 tables.- PMID: 19812389 [PubMed]
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 tanscription-independent (nongenomic) actions, consisting in the activation of signal transduction pathways, as the phosphatidyl-inositol-3-kinase or the ERK MAPK-signaling pathways. RA-induced rapid transcription-independent actions play a role in different physiological contexts. As an effort toward understanding the functions of those rapid actions on signaling elicited by RA, we have identified nuclear proteins the phosphorylation state of which 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: 1) those related to chromatin dynamics in relation to transcriptional activation, and 2) 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. Thus, our results underscore novel functions for the rapid signaling elicited by RAR in the regulation of mRNA processing. We conclude that RA activation of signaling pathways can indeed regulate mRNA processing as part of a cellular response orchestrated by the nuclear receptor RAR
This work was supported by grants of the Spanish former Ministry of Science and
Technology and Ministry of Education and Science (SAF2003-00311, SAF2006-00647 and
SAF2007-60780) and Generalitat Valenciana (ACOMP 06/212) to D. B.
Peer reviewed
2009-10-07
artículo
http://purl.org/coar/resource_type/c_6501
Molecular Endocrinology 23(11):1799-814 (2009)
0888-8809
http://hdl.handle.net/10261/31961
10.1210/me.2009-0165
1944-9917
19812389
en
http://dx.doi.org/10.1210/me.2009-0165
open
Endocrine Society