Ubiquitin signals are decoded in cells by at least 200 ubiquitin binding proteins, which interact with different types of polyubiquitin chains and ubiquitin-like modifiers. These interactions induce conformational changes that allow these proteins to transmit the ubiquitin signal to effector proteins (Dikic et al., 2009). Optineurin is a protein that is most closely related to NFκB Essential Modifier (NEMO) and, like NEMO, it contains a domain that binds to both Lys63-linked and linear polyubiquitin chains (Gleason et al.,2011). These polyubiquitin chains can then regulate downstream signaling events by inducing conformational changes that activate protein kinases such as IκB kinase (IKK) or Tank binding kinase (TBK1) (Gleason et al., 2011). TBK1 can also phosphorylate optineurin at Ser177, enhancing its interaction with the microtubule-associated protein light chain 3 (LC3) which in turn promotes the autophagic clearance of ubiquitylated cytosolic Salmonella (Wild et al., 2011). Mutations in optineurin cause three different diseases in humans, namely a form of glaucoma (Rezaie et al., 2002), Paget's disease of bone (Albagha et al., 2010) and amyotrophic lateral sclerosis (ALS), a form of motor neurone disease (Maruyama et al., 2010).The Optineurin [E478G] mutation, which causes ALS, abolishes binding to polyubiquitin chains (Gleason et al., 2011). Optineurin is a powerful reagent for capturing the Lys63-linked and linear polyubiquitin chains and their binding partners present in cell extracts. It is recommended that the Optineurin [D474N] mutant, which is unable to bind polyubiquitin chains, is used as a control in such experiments (Sudhakar et al., 2009).
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