Structure and functional properties of the ubiquitin binding protein p62

Abstract

Several highly conserved p62 homologs have recently been isolated, e.g. the rat atypical protein kinase C-interacting protein (ZIP), the murine A170/signal transduction and adapter protein, and the human p62, a protein that binds the Src homology 2 domain of p56(lck). These proteins share striking similarity in amino acid sequence and structural motifs, thereby suggesting conserved functional properties. ZIP/p62 has been shown to play an important role as a scaffold leading to the activation of the transcription factor nuclear factor kappaB. In addition, a nuclear form of p62 has been characterized that can serve as a transcriptional co-activator. Moreover, p62 is capable of binding ubiquitin (Ub) non-covalently through its Ub-associated domain. In this review, we will focus on the structure and function of ZIP/p62.