Interaction between hnRNPA1 and IkBa is required for maximal activation of NF-kB dependent transcription

Transcriptional activation of NF-kappaB is mediated by signal-induced phosphorylation and degradation of its inhibitor, I kappaB alpha. NF-kappaB activation a rapid induces a rapid resynthesis of I kappaB alpha which is responsible for postinduction repression of transcription. Following resynthesis, I kappaB alpha translocates to the nucleus, removes template bound NF-kappaB, and exports NF kappaB to the cytoplasm in a transcriptionally inactive form. Here we demonstrate that I kappaB alpha interacts directly with another nucleocytoplasmic shuttling protein, hnRNPA1, both in vivo and in vitro. This interaction requires one of the 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 defect in these cells is complemented by ectopic expression of hnRNPA1. hnRNPA1 expression in these cells increased the amount of IKBa degradation, compared to that of the control cells, in response to activation by EpsteinBarr virus latent membrane protein 1. Thus in addition to regulating mRNA processing and transport, hnRNPA1 also contributes to the control of NF-kappaB-dependent transcription.