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BMC Biol. 2012; 10: 23.
Published online Mar 15, 2012. doi:  10.1186/1741-7007-10-23
PMCID: PMC3305636
Generation and physiological roles of linear ubiquitin chains
Henning Walczak,corresponding author1 Kazuhiro Iwai,corresponding author2 and Ivan Dikiccorresponding author3
1Tumour Immunology Unit, Department of Medicine, Imperial College London, 10N5 Commonwealth Building, Du Cane Road, London W12 0NN, UK
2Department of Biophysics and Biochemistry, Graduate School of Medicine and Cell Biology and Metabolism Group, Graduate School of Frontier Biosciences, Osaka University 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
3Institute of Biochemistry II, Medical Faculty of the Goethe University, University Hospital Building 75, Theodor-Stern-Kai 7, 60528 Frankfurt am Main, Germany
corresponding authorCorresponding author.
Henning Walczak: h.walczak/at/imperial.ac.uk; Kazuhiro Iwai: kiwai/at/cellbio.med.osaka-u.ac.jp; Ivan Dikic: ivan.dikic/at/biochem2.de
Received November 21, 2011; Accepted March 15, 2012.
Abstract
Ubiquitination now ranks with phosphorylation as one of the best-studied post-translational modifications of proteins with broad regulatory roles across all of biology. Ubiquitination usually involves the addition of ubiquitin chains to target protein molecules, and these may be of eight different types, seven of which involve the linkage of one of the seven internal lysine (K) residues in one ubiquitin molecule to the carboxy-terminal diglycine of the next. In the eighth, the so-called linear ubiquitin chains, the linkage is between the amino-terminal amino group of methionine on a ubiquitin that is conjugated with a target protein and the carboxy-terminal carboxy group of the incoming ubiquitin. Physiological roles are well established for K48-linked chains, which are essential for signaling proteasomal degradation of proteins, and for K63-linked chains, which play a part in recruitment of DNA repair enzymes, cell signaling and endocytosis. We focus here on linear ubiquitin chains, how they are assembled, and how three different avenues of research have indicated physiological roles for linear ubiquitination in innate and adaptive immunity and suppression of inflammation.
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