Linear ubiquitin chain‐binding domains

• Published in: The FEBS journal 2018-08, Vol.285 (15), p.2746-2761
• Main Authors: Fennell, Lilian M., Rahighi, Simin, Ikeda, Fumiyo
• Format: Article
• Language: English
• Subjects: Animals; Autophagy; Binding; Binding Sites; Cascades; Catalytic Domain; Cell death; Chain branching; Chains; Ectodermal Dysplasia - genetics; Ectodermal Dysplasia - immunology; Homology; Humans; I-kappa B Kinase - genetics; I-kappa B Kinase - metabolism; Immune response; linear ubiquitin chain; Mutation; NZF; Phagocytosis; Protein Binding; Protein Domains; Proteins; Proteins - chemistry; Proteins - genetics; Proteins - metabolism; Signaling; Substrates; UBAN; Ubiquitin; Ubiquitin - metabolism; Ubiquitination; ubiquitin‐binding domain; Zinc Fingers
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.14478

Ubiquitin modification (ubiquitination) of target proteins can vary with respect to chain lengths, linkage type, and chain forms, such as homologous, mixed, and branched ubiquitin chains. Thus, ubiquitination can generate multiple unique surfaces on a target protein substrate. Ubiquitin‐binding domains (UBDs) recognize ubiquitinated substrates, by specifically binding to these unique surfaces, modulate the formation of cellular signaling complexes and regulate downstream signaling cascades. Among the eight different homotypic chain types, Met1‐linked (also termed linear) chains are the only chains in which linkage occurs on a non‐Lys residue of ubiquitin. Linear ubiquitin chains have been implicated in immune responses, cell death and autophagy, and several UBDs ‐ specific for linear ubiquitin chains ‐ have been identified. In this review, we describe the main principles of ubiquitin recognition by UBDs, focusing on linear ubiquitin chains and their roles in biology. Linear ubiquitination plays a regulatory role in the immune response, cell death, and autophagy. Recently, seven proteins which also play a role in these pathways, have been identified to contain linear ubiquitin chain‐binding domains. We summarize how these proteins interact with linear ubiquitin chains and highlight how human mutations identified in their ubiquitin‐binding domain may be implicated in human diseases.