Atypical ubiquitylation - the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages

Yogesh Kulathu, David Komander

    Research output: Contribution to journalArticlepeer-review

    529 Citations (Scopus)


    Ubiquitylation is one of the most abundant and versatile post-translational modifications (PTMs) in cells. Its versatility arises from the ability of ubiquitin to form eight structurally and functionally distinct polymers, in which ubiquitin moieties are linked via one of seven Lys residues or the amino terminus. Whereas the roles of Lys48- and Lys63-linked polyubiquitin in protein degradation and cellular signalling are well characterized, the functions of the remaining six 'atypical' ubiquitin chain types (linked via Lys6, Lys11, Lys27, Lys29, Lys33 and Met1) are less well defined. Recent developments provide insights into the mechanisms of ubiquitin chain assembly, recognition and hydrolysis and allow detailed analysis of the functions of atypical ubiquitin chains. The importance of Lys11 linkages and Met1 linkages in cell cycle regulation and nuclear factor-?B activation, respectively, highlight that the different ubiquitin chain types should be considered as functionally independent PTMs.
    Original languageEnglish
    Pages (from-to)508-523
    Number of pages16
    JournalNature Reviews Molecular Cell Biology
    Issue number8
    Publication statusPublished - Aug 2012


    • Proteolysis
    • Ubiquitin-Protein Ligases
    • NF-kappa B
    • Humans
    • Proteasome Endopeptidase Complex
    • Polyubiquitin
    • Ubiquitination
    • Lysine
    • Hydrolysis
    • Cell Cycle
    • Signal Transduction


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