TNF- production is regulated by transcriptional and post-transcriptional mechanism. LPS activates the NFB pathway increasing TNF- transcription. LPS also activates the MAP Kinase pathways resulting in stabilization and enhanced translation of the TNF- message. In addition, nuclear export of the TNF- mRNA is a regulated posttranscriptional process involving the Tpl2-ERK pathway and requiring the presence of the TNF- AU-Rich Element (ARE). We demonstrate that nuclear export of the TNF- message requires not only the TNF- AU-Rich Element but also the interaction of the proteins TAP and NxT1, both of which are involved in nucleo-cytoplasmic transport of mRNA. Through the use of dominant negative ERK1 and ERK2, we establish that control of TNF- mRNA nuclear export operates specifically through ERK1. Finally, we examined the role of two established TNF- ARE binding proteins, HuR and TTP, that shuttle between the nucleus and cytoplasm. These data demonstrate that neither TTP nor HuR is required for TNF- mRNA export. It is unclear at this time if ARE binding protein(s) directly interact with the TAP/NxT1 complex or if each complex is independently targeted by ERK1.