Linear ubiquitin chains: Enzymes, mechanisms and biology

Katrin Rittinger, Fumiyo Ikeda

Research output: Contribution to journalReview article

29 Citations (Scopus)

Abstract

Ubiquitination is a versatile post-translational modification that regulates a multitude of cellular processes. Its versatility is based on the ability of ubiquitin to form multiple types of polyubiquitin chains, which are recognized by specific ubiquitin receptors to induce the required cellular response. Linear ubiquitin chains are linked through Met 1 and have been established as important players of inflammatory signalling and apoptotic cell death. These chains are generated by a ubiquitin E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) that is thus far the only E3 ligase capable of forming linear ubiquitin chains. The complex consists of three subunits, HOIP, HOIL-1L and SHARPIN, each of which have specific roles in the observed biological functions of LUBAC. Furthermore, LUBAC has been found to be associated with OTULIN and CYLD, deubiquitinases that disassemble linear chains and counterbalance the E3 ligase activity of LUBAC. Gene mutations in HOIP, HOIL-1L and OTULIN are found in human patients who suffer from autoimmune diseases, and HOIL-1L mutations are also found in myopathy patients. In this paper, we discuss the mechanisms of linear ubiquitin chain generation and disassembly by their respective enzymes and review our current understanding of their biological functions and association with human diseases.

Original languageEnglish
Article number170026
JournalOpen Biology
Volume7
Issue number4
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Ubiquitin
Enzymes
Ubiquitin-Protein Ligases
Polyubiquitin
Mutation
Ubiquitination
Muscular Diseases
Cell death
Post Translational Protein Processing
Autoimmune Diseases
Cell Death
Genes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Linear ubiquitin chains : Enzymes, mechanisms and biology. / Rittinger, Katrin; Ikeda, Fumiyo.

In: Open Biology, Vol. 7, No. 4, 170026, 01.01.2017.

Research output: Contribution to journalReview article

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