THE ROLE OF TIGHT JUNCTION PROTEIN ZO-2 IN THE NUCLEUS AND ITS LINK TO TRANSCRIPTION FACTORS OF THE SLUG/SNAIL FAMILY

Abstract

ZO-2 is an adaptor protein that is associated with the transmembrane proteins of the tight junction (TJ). It is capable of shuttling between the TJ and the nucleus and is known to participate in gene regulation through its association with gene regulators. To identify proteins interacting with ZO-2, a yeast two-hybrid screen was carried out and a transcription factor was isolated as a novel interacting partner. This transcription factor was shown to possess functional nuclear localization signals, nuclear export signal and zinc fingers that are important for DNA binding and nuclear retention. Furthermore, ZO-2 may also influence the sub-cellular localization of this transcription factor, for example in wound healing assays. Wounding of the cell monolayer raises the nuclear levels of both ZO-2 and this transcription factor, while closure of the wound and high cell confluency lead to the recruitment of ZO-2 back to the TJ and the rapid degradation of its partner. Based on the ability to manipulate the stability and localization of this transcription factor by various ZO-2 constructs, we postulate that ZO-2 can sequester this transcription factor within the nucleus to sequester it from degradation by the proteasome in the cytosol. This model is placed in context with our current understanding of epithelial-to-mesenchymal transition and would be important in processes such as cell migration during developmental processes, wound healing and cancer.