Interaction between hnRNPA1 and I kappa B alpha is required for maximal activation of NF-kappa B-dependent transcription

Transcriptional activation of NF-kappaB is mediated by signal-induced phosp horylation and degradation of its inhibitor, I kappaB alpha. NF-kappaB acti vation a rapid induces a rapid resynthesis of I kappaB alpha which is respo nsible for postinduction repression of transcription. Following resynthesis , I kappaB alpha translocates to the nucleus, removes template bound NF-kap paB, and exports NF kappaB to the cytoplasm in a transcriptionally inactive form. Here we demonstrate that I kappaB alpha interacts directly with anot her nucleocytoplasmic shuttling protein, hnRNPA1, both in vivo and in vitro . This interaction requires one of tile N-terminal RNA. binding domains of hnRNPA1 and the C terminal region of I kappaB alpha. Cells lacking hnRNPA1 are defective in NF-kappaB-dependent transcriptional activation, but the de fect in these cells is complemented by ectopic expression of hnRNPA1. hnRNP A1 expression in these cells increased the amount of IKBa degradation, comp ared to that of the control cells, in response to activation by EpsteinBarr virus latent membrane protein 1, Thus in addition to regulating mRNA proce ssing and transport, hnRNPA1 also contributes to the control of NF-kappaB-d ependent transcription.