title: Selective protein degradation in cell signalling.
abstract: A variety of post-translational modifications such as phosphorylation, acetylation and ubiquitylation transduce cellular signals, which culminate in changes in gene transcription. In this article we examine the ways in which selective protein degradation provides an extra dimension to the regulation of such signalling cascades. We discuss (i) how both lysosomal and proteasomal systems are used to attenuate kinase and rho family GTPase signalling, thereby coupling activation with degradation, (ii) signal propagation contingent upon the selective degradation of inhibitory components, exemplified by the degradation of IκB to activate NF-κB signalling, and (iii) tonic suppression of signalling pathways by turnover of the transcription factors β-catenin and p53.
authors.affiliation: Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3BX, UK. liuhan@liv.ac.uk
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.forename: Sylvie
authors.initials: S
authors.lastname: Urbé
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clague
mesh_terms: D000818:Animals; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D059748:Proteolysis; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D011494:Protein Kinases