首页|Met1-linked ubiquitination in cell signaling regulation
Met1-linked ubiquitination in cell signaling regulation
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Met1-linked ubiquitination(Met1-Ub),also known as linear ubiquitination,is a newly identified atypi-cal type of polyubiquitination that is assembled via the N-terminal methionine(Met1)rather than an internal lysine(Lys)residue of ubiquitin.The linear ubiquitin chain assembly complex(LUBAC)com-posed of HOIP,HOIL-1L and SHARPIN is the sole E3 ubiquitin ligase that specifically generates Met1-linked ubiquitin chains.The physiological role of LUBAC-mediated Met1-Ub has been first described as activating NF-κB signaling through the Met1-Ub modification of NEMO.However,accumulating evi-dence shows that Met1-Ub is broadly involved in other cellular pathways including MAPK,Wnt/β-Catenin,PI3K/AKT and interferon signaling,and participates in various cellular processes including an-giogenesis,protein quality control and autophagy,suggesting that Met1-Ub harbors a potent signaling capacity.Here,we review the formation and cellular functions of Met1-linked ubiquitin chains,with an emphasis on the recent advances in the cellular mechanisms by which Met1-Ub controls signaling transduction.
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