Sequestosome 1/p62: a multi-domain protein with multi-faceted functions

Abstract

The sequestosome 1/p62 protein has been implicated in the regulation of a multitude of cellular processes such as NF-кB signaling, NRF2-driven oxidative stress response, protein turnover through the ubiquitin-proteasome pathway and the autophagosome/lysosome pathway, apoptosis and cellular metabolism. The domain structure of p62 also reflects this functional complexity since the protein appears to be a mosaic of protein interaction domains and motifs. Deregulation of the level and function of p62 and/or p62 mutations have been linked to a number of human diseases including Paget’s disease of the bone, obesity, liver diseases, tumorigenesis and neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer’s disease. In this article, we review the current understanding of the involvement of p62 in cellular processes under physiologic and pathological conditions.

Keywords

sequestosome 1/p62 / autophagy / ubiquitin-proteasome system / NF-κB signaling / Paget′s disease of bone / amyotrophic lateral sclerosis

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Acknowledgments

This study was in part supported by NIH grant R21-AG032567 to H. Z.

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg