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 journalReview articlepeer-review

3 Citations (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
Pages (from-to)285-292
Number of pages8
JournalArchives of pharmacal research
Issue number4
Publication statusPublished - 2019 Apr 1

Bibliographical note

Funding Information:
Acknowledgements This work was supported by National Research Foundation of Korea (NRF) Grants funded by the Korea Government Ministry of Science and ICT (NRF-2018R1C1B6001235, NRF-2018M3C7A1024603, NRF-2018R1A6A3A11040508).

Publisher Copyright:
© 2018, The Pharmaceutical Society of Korea.


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

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Organic Chemistry


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