Emerging roles of Lys63-linked polyubiquitination in neuronal excitatory postsynapses

Shinhyun Kim, Yinhua Zhang, Chunmei Jin, Yeunkum Lee, Yoonhee Kim, Kihoon Han

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


In the mammalian brain, neuronal excitatory synaptic development, function, and plasticity largely rely on dynamic, activity-dependent changes in the macromolecular protein complex called the postsynaptic density (PSD). Activity-dependent Lys48-linked polyubiquitination and subsequent proteasomal degradation of key proteins in the PSD have been reported. However, investigations into the functions and regulatory mechanisms of Lys63-linked polyubiquitination, the second most abundant polyubiquitin form in synapses, have recently begun. Recent studies showed that a Lys63 linkage-specific deubiquitinase (DUB), cylindromatosis-associated DUB (CYLD) localizes to the PSD where its DUB activity is regulated by different kinases. In addition, Lys63-linked polyubiquitination of postsynaptic density 95 (PSD-95), a core scaffolding protein of the PSD, was identified and its functional significance in synaptic plasticity was characterized. In this review, we summarize these recent findings on Lys63-linked polyubiquitination in excitatory postsynapses, and also propose key questions and prospects about this emerging type of posttranslational modification of the PSD proteome.

Original languageEnglish
JournalArchives of Pharmacal Research
Publication statusAccepted/In press - 2018 Jan 1


  • CYLD
  • Excitatory postsynapse
  • Lys63-linked polyubiquitination
  • Postsynaptic density
  • PSD-95

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry

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