1. ¹Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA
2. ²Department of Biological Sciences and Program in Cellular and Molecular Biosciences, Auburn University, Auburn, Alabama, USA

Correspondence: J Moscat, Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, The Vontz Center for Molecular Studies, 3125 Eden Avenue, Cincinnati, OH 45267, USA. Tel: 513 558 8419; Fax: 513 558 2445; E-mail: jorge.moscat@uc.edu

Received 23 April 2009; Revised 9 July 2009; Accepted 21 July 2009; Published online 28 August 2009.

Abstract

The recent identification of a novel protein–protein interaction module, termed PB1, in critical signaling molecules such as p62 (also known as sequestosome1), the atypical PKCs, and Par-6, has unveiled the existence of a new set of signaling complexes, which can be central to several biological processes from development to cancer. In this review, we will discuss the most recent advances on the role that the different components of these complexes have in vivo and that are relevant to human disease. In particular, we will review what we are learning from new data from knockout mice, and the indications from human mutations on the real role of these proteins in the physiology and biology of human diseases. The role that PKC, PKC/, and Par-4 have in lung and prostate cancer in vivo and in humans will be extensively covered in this article, as will the multifunctional role of p62 as a novel hub in cell signaling during cancer and inflammation, and the mechanistic details and controversial data published on its potential role in aggregate formation and signaling. All this published information is shedding new light on the proposed pathological implications of these PB1-regulators in disease and shows their important role in cell physiology.