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The molecular machinery that assembles, senses and, more recently, disassembles Met1\u2010Ub has been identified, and technical advances have enabled the identification of physiological substrates for Met1\u2010Ub in response to activation of innate immune receptors. These discoveries have significantly advanced our understanding of how nondegradative ubiquitin modifications control proinflammatory responses mediated by nuclear factor\u2010\u03baB and mitogen\u2010activated protein kinases. 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