Adapter protein NRBP associates with Jab1 and negatively regulates AP-1 activity.

Jun activation domain-binding protein 1 (Jab1) is a coactivator of activating protein-1 (AP-1) and is the fifth component of the COP9 signalosome complex. It interacts with a variety of proteins and plays important roles in diverse signaling pathways and cellular function including oncogenesis. We show here that Jab1 interacts in vivo with nuclear receptor binding protein (NRBP), an evolutionarily conserved adapter protein with a kinase-like domain. We further show that NRBP inhibits Jab1-induced phosphorylation of c-Jun and AP-1 activation. Finally, overexpression of NRBP in mammalian cells specifically inhibits AP-1 activation by various stimuli. Taken together, our data suggest that NRBP may be an important negative regulator of Jab1-mediated functions such as gene transcription and tumor progression.