TAZ interacts with zonula occludens-1 and -2 proteins in a PDZ-1 dependent manner.

The transcriptional coactivator TAZ recognizes L/PPxY motifs in transcription factors like Runx1/2 through its WW domain. We show that the first PDZ domain of zona occludens-1 (ZO-1) and 2 (ZO-2) interacts with the carboxy-terminal PDZ binding motif of TAZ. Deletion of this motif abrogates binding. ZO-2 colocalizes with TAZ in the nucleus of MDCK cells and ZO-2 expression alters TAZ localization in human embryonic kidney cells. Luciferase assays demonstrate ZO-2 inhibition of TAZ-mediated transactivation. We propose that zonula occludens is a negative regulator of TAZ and suggest that selected tight junction proteins control nuclear translocation and activity of TAZ.