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Misfolded polypeptides are selectively recognized and transported toward aggresomes by a CED complex

Author

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  • Joori Park

    (Creative Research Initiatives Center for Molecular Biology of Translation, Korea University
    Korea University)

  • Yeonkyoung Park

    (Creative Research Initiatives Center for Molecular Biology of Translation, Korea University
    Korea University)

  • Incheol Ryu

    (Creative Research Initiatives Center for Molecular Biology of Translation, Korea University
    Korea University)

  • Mi-Hyun Choi

    (Korea University)

  • Hyo Jin Lee

    (Korea University)

  • Nara Oh

    (Creative Research Initiatives Center for Molecular Biology of Translation, Korea University
    Korea University)

  • Kyutae Kim

    (Korea University
    BRI, Korea Institute of Science and Technology)

  • Kyoung Mi Kim

    (Korea University
    Present address: Laboratory of Genetics and Genomics, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA)

  • Junho Choe

    (Korea University
    Present address: Stem Cell Program, Boston Children’s Hospital, Massachusetts 02115, USA)

  • Cheolju Lee

    (BRI, Korea Institute of Science and Technology)

  • Ja-Hyun Baik

    (Korea University)

  • Yoon Ki Kim

    (Creative Research Initiatives Center for Molecular Biology of Translation, Korea University
    Korea University)

Abstract

Misfolded polypeptides are rapidly cleared from cells via the ubiquitin–proteasome system (UPS). However, when the UPS is impaired, misfolded polypeptides form small cytoplasmic aggregates, which are sequestered into an aggresome and ultimately degraded by aggrephagy. Despite the relevance of the aggresome to neurodegenerative proteinopathies, the molecular mechanisms underlying aggresome formation remain unclear. Here we show that the CTIF–eEF1A1–DCTN1 (CED) complex functions in the surveillance of either pre-existing or newly synthesized polypeptides by linking two molecular events: selective recognition and aggresomal targeting of misfolded polypeptides. These events are accompanied by CTIF sequestration into the aggresome, preventing the additional synthesis of misfolded polypeptides from mRNAs bound by nuclear cap-binding complex. These events render cells more resistant to apoptosis induced by proteotoxic stresses. Collectively, our data provide compelling evidence for a previously unappreciated protein surveillance pathway and a regulatory gene expression network for coping with misfolded polypeptides.

Suggested Citation

  • Joori Park & Yeonkyoung Park & Incheol Ryu & Mi-Hyun Choi & Hyo Jin Lee & Nara Oh & Kyutae Kim & Kyoung Mi Kim & Junho Choe & Cheolju Lee & Ja-Hyun Baik & Yoon Ki Kim, 2017. "Misfolded polypeptides are selectively recognized and transported toward aggresomes by a CED complex," Nature Communications, Nature, vol. 8(1), pages 1-15, August.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15730
    DOI: 10.1038/ncomms15730
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    Cited by:

    1. Hyun Jung Hwang & Tae Lim Park & Hyeong-In Kim & Yeonkyoung Park & Geunhee Kim & Chiyeol Song & Won-Ki Cho & Yoon Ki Kim, 2023. "YTHDF2 facilitates aggresome formation via UPF1 in an m6A-independent manner," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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