hnRNP A1 regulates UV-induced NF-kappaB signalling through destabilization of cIAP1 mRNA.
cIAP1 is an important member of the inhibitor of apoptosis family of proteins and is involved in the regulation of the NF-kappaB-signalling 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' untranslated region of cIAP1 mRNA is sufficient to mediate cIAP1 mRNA instability. Furthermore, we have identified hnRNP A1 as a cIAP1 3'UTR-binding protein. 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, siRNA-mediated knockdown of hnRNP A1 restores cIAP1 levels and prevents UV irradiation-induced activation of the NF-kappaB signal transduction pathway, suggesting that hnRNP A1 is an essential post-transcriptional modulator of cIAP1 expression, and thus cIAP1 activity.
Zhao
T T
TT
Apoptosis Research Centre, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, Canada K1H 8L1.
Graber
T E
TE
Jordan
L E
LE
Cloutier
M
M
Lewis
S M
SM
Goulet
I
I
Côté
J
J
Holcik
M
M
D020413:3' Untranslated Regions / Q000378:metabolism; D002460:Cell Line; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D016328:NF-kappa B / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism* / Q000528:radiation effects; D034741:RNA, Small Interfering; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D014466:Ultraviolet Rays
D020413:3' Untranslated Regions; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018124:Receptors, Tumor Necrosis Factor