Cereblon is recruited to aggresome and shows cytoprotective effect against ubiquitin-proteasome system dysfunction

Naoya Sawamura, Satoru Wakabayashi, Kodai Matsumoto, Haruka Yamada, Toru Asahi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Cereblon (CRBN) is encoded by a candidate gene for autosomal recessive nonsyndromic intellectual disability (ID). The nonsense mutation, R419X, causes deletion of 24 amino acids at the C-terminus of CRBN, leading to mild ID. Although abnormal CRBN function may be associated with ID disease onset, its cellular mechanism is still unclear. Here, we examine the role of CRBN in aggresome formation and cytoprotection. In the presence of a proteasome inhibitor, exogenous CRBN formed perinuclear inclusions and co-localized with aggresome markers. Endogenous CRBN also formed perinuclear inclusions under the same condition. Treatment with a microtubule destabilizer or an inhibitor of the E3 ubiquitin ligase activity of CRBN blocked formation of CRBN inclusions. Biochemical analysis showed CRBN containing inclusions were high-molecular weight, ubiquitin-positive. CRBN overexpression in cultured cells suppressed cell death induced by proteasome inhibitor. Furthermore, knockdown of endogenous CRBN in cultured cells increased cell death induced by proteasome inhibitor, compared with control cells. Our results show CRBN is recruited to aggresome and has functional roles in cytoprotection against ubiquitin-proteasome system impaired condition.

Original languageEnglish
Pages (from-to)1054-1059
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume464
Issue number4
DOIs
Publication statusPublished - 2015 Sep 4

Fingerprint

Proteasome Inhibitors
Proteasome Endopeptidase Complex
Ubiquitin
Intellectual Disability
Cytoprotection
Cultured Cells
Cell Death
Cell death
Recessive Genes
Ubiquitin-Protein Ligases
Nonsense Codon
Cells
Microtubules
Molecular Weight
Amino Acids
Genes
Molecular weight

Keywords

  • Aggresome
  • Cereblon
  • Cytoprotection
  • Intellectual disability
  • Ubiquitin-proteasome system

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Cereblon is recruited to aggresome and shows cytoprotective effect against ubiquitin-proteasome system dysfunction. / Sawamura, Naoya; Wakabayashi, Satoru; Matsumoto, Kodai; Yamada, Haruka; Asahi, Toru.

In: Biochemical and Biophysical Research Communications, Vol. 464, No. 4, 04.09.2015, p. 1054-1059.

Research output: Contribution to journalArticle

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