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The linear ubiquitin chain assembly complex, LUBAC, is the only known mammalian ubiquitin ligase that makes methionine 1 (Met1)-linked polyubiquitin (also referred to as linear ubiquitin). A decade after LUBAC was discovered as a cellular activity of unknown function, there are now many lines of evidence connecting Met1-linked polyubiquitin to NF-κB signaling, cell death, inflammation, immunity, and cancer. We now know that Met1-linked polyubiquitin has potent signaling functions and that its deregulation is connected to disease. Indeed, mutations and deficiencies in several factors involved in conjugation and deconjugation of Met1-linked polyubiquitin have been implicated in immune-related disorders. Here, we discuss current knowledge and recent insights into the role and regulation of Met1-linked polyubiquitin, with an emphasis on the mechanisms controlling the function of LUBAC.

Original publication

DOI

10.1016/j.molcel.2017.09.001

Type

Journal article

Journal

Mol Cell

Publication Date

19/10/2017

Volume

68

Pages

265 - 280

Keywords

CYLD, LUBAC, Met1-linked ubiquitin, OTULIN, SPATA2, cancer, caspases, host-pathogen interaction, immune disorders, linear ubiquitin, Animals, Cell Death, Humans, Immunity, NF-kappa B, Neoplasm Proteins, Neoplasms, Polyubiquitin, Signal Transduction