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  • 标题:Nuclear export of ubiquitinated proteins via the UBIN-POST system
  • 本地全文:下载
  • 作者:Shoshiro Hirayama ; Munechika Sugihara ; Daisuke Morito
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2018
  • 卷号:115
  • 期号:18
  • 页码:E4199-E4208
  • DOI:10.1073/pnas.1711017115
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Although mechanisms for protein homeostasis in the cytosol have been studied extensively, those in the nucleus remain largely unknown. Here, we identified that a protein complex mediates export of polyubiquitinated proteins from the nucleus to the cytosol. UBIN, a ubiquitin-associated (UBA) domain-containing protein, shuttled between the nucleus and the cytosol in a CRM1-dependent manner, despite the lack of intrinsic nuclear export signal (NES). Instead, the UBIN binding protein polyubiquitinated substrate transporter (POST) harboring an NES shuttled UBIN through nuclear pores. UBIN bound to polyubiquitin chain through its UBA domain, and the UBIN-POST complex exported them from the nucleus to the cytosol. Ubiquitinated proteins accumulated in the cytosol in response to proteasome inhibition, whereas cotreatment with CRM1 inhibitor led to their accumulation in the nucleus. Our results suggest that ubiquitinated proteins are exported from the nucleus to the cytosol in the UBIN-POST complex-dependent manner for the maintenance of nuclear protein homeostasis.
  • 关键词:protein quality control ; ubiquitin ; protein aggregation ; protein transport
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