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Báo cáo Y học: Evidence for general stabilization of mRNAs in response to UV light

mRNA stabilization plays an important role in the changes in protein expression initiated by inducers of inflammation or direct cell stress such as UV light. This study provides evidence that stabilization in response to UV light differs from that induced by proinflammatory stimuli such as bacterial lipopolysaccharide or interleukin (IL)-1. Firstly, UV-induced stabilization is independent of the p38 MAP kinase pathway, which has previously been shown to medi-ate stabilization induced by IL-1 or lipopolysaccharide | Eur. J. Biochem. 269 5830-5839 2002 FEBS 2002 doi 10.1046 j.1432-1033.2002.03300.x Evidence for general stabilization of mRNAs in response to UV light Frank Bollig Reinhard Winzen Michael Kracht Beniam Ghebremedhin Birgit Ritter Arno Wilhelm Klaus Resch and Helmut Holtmann Institute of Pharmacology Medical School Hannover Germany mRNA stabilization plays an important role in the changes in protein expression initiated by inducers of inflammation or direct cell stress such as UV light. This study provides evidence that stabilization in response to UV light differs from that induced by proinflammatory stimuli such as bacterial lipopolysaccharide or interleukin IL -1. Firstly UV-induced stabilization is independent of the p38 MAP kinase pathway which has previously been shown to mediate stabilization induced by IL-1 or lipopolysaccharide. UV-induced mRNA stabilization was insensitive to the dominant negative forms of p38 MAP kinase and its substrate MAP kinase-activated protein kinase 2 MK2 or to the p38 MAP kinase inhibitor SB 203580 demonstrating that it occurs through a different signaling mechanism. Secondly UV-induced stabilization exhibits a different transcript selectivity. Activation of the p38 MAP kinase pathway by expressing active MAP kinase kinase 6 induced stabilization only of transcripts containing AU-rich elements. UV light also induced stabilization of transcripts lacking AU-rich elements. This effect could not be mimicked by expressing MEKK1 an upstream activator of the p38 JNK ERK and NF-kB pathways. UV light also stabilized endogenous histone mRNA which lacks AU-rich elements and a poly A tail. This effect was not mimicked by active MAP kinase kinase 6 and not sensitive to a p38 MAP kinase inhibitor. This suggests that UV light induces stabilization through a mechanism that is independent of p38 MAP kinase and affects a broad spectrum of mRNAs. Keywords AU-rich element MAPKAP kinase 2 mRNA stability p38 MAP kinase UV light. Higher organisms respond