When Worlds Collide—Mechanisms at the Interface between Phosphorylation and Ubiquitination. Issue 8 (21st April 2017)

• Record Type: Journal Article
• Authors: Filipčík, Pavel; Curry, Jack R.; Mace, Peter D.
• Is Part Of: Journal of molecular biology. Volume 429:Issue 8(2017)
• Page Start: 1097
• Page End: 1113
• Publication Date: 2017-04-21
• Subjects: PTM post-translational modification -- RBR RING-between-RING -- DUB deubiquitinase -- USP ubiquitin-specific protease -- SCF Skp1-Cullin-F-box -- CaMKII Ca2 +/calmodulin-dependent kinase 2 -- Cbl Casitas B-lineage lymphoma -- TKB tyrosine kinase binding -- RTK receptor tyrosine kinase -- APC/C anaphase-promoting complex or cyclosome -- NLS nuclear localisation signal -- PINK1 PTEN-induced kinase 1 -- SUMO small ubiquitin-like modifier -- SIM SUMO-interacting domain -- PML promyelocytic leukaemia -- TBK1 TANK-binding kinase 1 -- HOIP HOIL-1-interacting protein -- ATM ataxia telangiectasia mutated; E3 ubiquitin ligase -- kinase -- phosphodegron -- deubiquitinase -- phosphoubiquitin; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2017.02.011
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Phosphorylation and ubiquitination are pervasive post-translational modifications that impact all processes inside eukaryotic cells. The role of each modification has been studied for decades, and functional interplay between the two has long been demonstrated and even more widely postulated. However, our understanding of the molecular features that allow phosphorylation to control protein ubiquitination and ubiquitin to control phosphorylation has only recently begun to build. Here, we review examples of regulation between ubiquitination and phosphorylation, aiming to describe mechanisms at the molecular level. In general, these examples illustrate phosphorylation as a versatile switch throughout ubiquitination pathways, and ubiquitination primarily impacting kinase signalling in a more emphatic manner through scaffolding or degradation. Examples of regulation between these two processes are likely to grow even further as advances in molecular biology, proteomics, and computation allow a system-level understanding of signalling. Many new cases could involve similar principles to those described here, but the extensive co-regulation of these two systems leaves no doubt that they still have many surprises in store. Graphical Abstract: Highlights: Dynamic kinase-based control of E3 ubiquitin ligases Flexible mechanisms of substrate recognition through phosphodegrons Modulation of ubiquitin disassembly by deubiquitinase phosphorylation Phosphorylation of Ub and Ubls has profound effects on mitophagy. Regulation of kinase conformation by site-specific ubiquitination