hnRNP A1 regulates UV-induced NF-κB signalling through destabilization of cIAP1 mRNA

T T Zhao, T E Graber, L E Jordan, M Cloutier, S M Lewis, I Goulet, J Côté, M Holcik
2008 Cell Death and Differentiation  
cIAP1 is an important member of the inhibitor of apoptosis family of proteins and is involved in the regulation of the NF-jBsignalling pathway downstream of the TNF receptor. We report here that UV irradiation leads to downregulation of cIAP1 expression because of enhanced cIAP1 mRNA destabilization. An AU-rich element located within the 3 0 untranslated region of cIAP1 mRNA is sufficient to mediate cIAP1 mRNA instability. Furthermore, we have identified hnRNP A1 as a cIAP1 3 0 UTR-binding
more » ... in. hnRNP A1 is a primarily nuclear protein, but accumulates in the cytoplasm after exposure of cells to UV irradiation. Indeed, we find that hnRNP A1 enhances the destabilization of cIAP1 mRNA during UV irradiation. Moreover, siRNAmediated knockdown of hnRNP A1 restores cIAP1 levels and prevents UV irradiation-induced activation of the NF-jB signal transduction pathway, suggesting that hnRNP A1 is an essential post-transcriptional modulator of cIAP1 expression, and thus cIAP1 activity.
doi:10.1038/cdd.2008.146 pmid:18846111 fatcat:pifot3gb2zc6reqzehqkb6pzju