LUBAC binds OTULIN

The linear ubiquitin (Ub) chain assembly complex (LUBAC) is an E3 ligase that specifically assembles Met1-linked (also known as linear) Ub chains that regulate nuclear factor kappa-B (NF-kappa-B) signaling. Deubiquitinases are key regulators of Ub signaling. OTULIN (also known as FAM105B) is an OTU domain deubiquitinase which specifically disassembles Met1-linked polyUb generated by LUBAC (Keusekotten K et al. 2013; Rivkin E et al. 2013). OTULIN antagonizes processes involving LUBAC, including tumor necrosis factor alpha (TNFalpha), poly(I:C), NOD2 and Wnt signaling (Fiil BK et al. 2013; Keusekotten K et al. 2013; Rivkin E et al. 2013). OTULIN interacts directly with the N-terminal PUB domain of HOIP, a component of the LUBAC complex, via a conserved PUB-interacting motif (PIM) in OTULIN (Elliott PR et al. 2014; Schaeffer V et al. 2014). Furthermore, OTULIN phosphorylation at Tyr56 within PIM was found to prevent the LUBAC:OTULIN complex formation (Elliott PR et al. 2014).

线性泛素（Ub）链组装复合物（LUBAC）是一种E3连接酶，它专门组装与Met1链接的（亦称为线性）泛素链，这些链调节核因子κ-B（NF-κ-B）信号传导。去泛素化酶是泛素信号传导的关键调节因子。OTULIN（亦称为FAM105B）是一种OTU结构域去泛素化酶，它专门分解由LUBAC产生的Met1链接的多泛素（Keusekotten K等人，2013；Rivkin E等人，2013）。OTULIN拮抗涉及LUBAC的过程，包括肿瘤坏死因子α（TNFα）、聚（I:C）、NOD2和Wnt信号传导（Fiil BK等人，2013；Keusekotten K等人，2013；Rivkin E等人，2013）。OTULIN通过OTULIN中的保守PUB相互作用基序（PIM）直接与LUBAC复合物成分HOIP的N端PUB结构域相互作用（Elliott PR等人，2014；Schaeffer V等人，2014）。此外，发现OTULIN在PIM中的Tyr56位点的磷酸化可防止LUBAC:OTULIN复合物的形成（Elliott PR等人，2014）。