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

Kulathu, Yogesh, Komander, David·2012·Nature Reviews Molecular Cell Biology
DOI 10.1038/nrm3394
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Abstract

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-κB activation, respectively, highlight that the different ubiquitin chain types should be considered as functionally independent PTMs.

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  • Chains linked via one of the other six lysines in ubiquitin can protect modified substrates from proteasomal degradation and divert them toward functions including trafficking, signaling, and autophagy.

    “In contrast, chains linked via one of the other six lysines in Ub can protect modified substrates from proteasomal degradation and divert them toward functions in a variety of cellular pathways including trafficking, signaling, and autophagy (Komander & Rape, 2012;Kulathu & Komander, 2012).”

    From USP8 regulates mitophagy by removing K6‐linked ubiquitin conjugates from parkin (2014) · cites this paper as Kulathu & Komander, 2012

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Metadata

Authors
Kulathu, Y., & Komander, D.
Venue
Nature Reviews Molecular Cell Biology
Publisher
Springer Science and Business Media LLC
Published
2012-07-23
Volume
13
Issue
8
Pages
508-523
ISSN
  • 1471-0072
  • 1471-0080
DOI
10.1038/nrm3394
Cited by
619
References
8
Language
en
Licence
www.springer.com/tdm (tdm)

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