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Sci. Signal., 20 December 2011
Vol. 4, Issue 204, p. re5
[DOI: 10.1126/scisignal.2002187]

REVIEWS

The Emerging Role of Linear Ubiquitination in Cell Signaling

Christoph H. Emmerich*, Anna C. Schmukle*, and Henning Walczak{dagger}

Tumour Immunology Unit, Department of Medicine, Imperial College London, London W12 0NN, UK.
* These authors contributed equally to this work.

Gloss: To ensure appropriate responses of cells to external stimuli, the intracellular events that initiate these reactions must be tightly controlled. Different mechanisms ensure this regulation. One possibility involves the attachment of regulatory elements onto components of signal-initiating complexes. One form of modification is the attachment of particular cellular proteins, an example of which is the covalent coupling of ubiquitin to a target protein by a specialized enzymatic system, a process called ubiquitination. Such modifications have different functions, ranging from the recruitment of other binding partners to the activation or inactivation of the substrate. Ubiquitination can attach single ubiquitin molecules and chains consisting of several ubiquitin moieties to target proteins. Depending on how the single ubiquitin units within these chains are linked, their structure and consequently their function differ. It was originally thought that only seven different types of polyubiquitin chains could be generated, based on the seven lysine residues in ubiquitin that serve as internal linkage points. However, a protein complex called linear ubiquitin chain assembly complex (LUBAC) was discovered that uses the N terminus of ubiquitin, rather than an internal lysine, thereby forming linear or M1-linked ubiquitin chains. LUBAC and linear ubiquitin chains are important for transmitting signals induced by diverse stimuli that regulate cell activation and death. In this Review, which contains two figures, one table, and 105 references, we discuss the functional role of LUBAC and the linear ubiquitin chains it generates, and we provide an outlook on promising future research directions.

{dagger} Corresponding author. Division of Immunology and Inflammation, Imperial College London, Hammersmith Hospital, Commonwealth Building, Du Cane Road, London W12 0NN, UK. E-mail: h.walczak{at}imperial.ac.uk

Citation: C. H. Emmerich, A. C. Schmukle, H. Walczak, The Emerging Role of Linear Ubiquitination in Cell Signaling. Sci. Signal. 4, re5 (2011).

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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J. Cell Sci. 125, 549-559
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