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

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Article number15730
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 2017 Jun 7

Fingerprint

polypeptides
Peptides
Proteasome Endopeptidase Complex
surveillance
Ubiquitin
Gene Regulatory Networks
gene expression
apoptosis
Regulator Genes
cells
Gene expression
caps
Apoptosis
proteins
Gene Expression
Messenger RNA
synthesis
Proteins

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Misfolded polypeptides are selectively recognized and transported toward aggresomes by a CED complex. / Park, Joori; Park, Yeonkyoung; Ryu, Incheol; Choi, Mi Hyun; Lee, Hyo Jin; Oh, Nara; Kim, Kyutae; Kim, Kyoung Mi; Choe, Junho; Lee, Cheolju; Baik, Ja-Hyun; Kim, Yoon Ki.

In: Nature Communications, Vol. 8, 15730, 07.06.2017.

Research output: Contribution to journalArticle

Park, Joori ; Park, Yeonkyoung ; Ryu, Incheol ; Choi, Mi Hyun ; Lee, Hyo Jin ; Oh, Nara ; Kim, Kyutae ; Kim, Kyoung Mi ; Choe, Junho ; Lee, Cheolju ; Baik, Ja-Hyun ; Kim, Yoon Ki. / Misfolded polypeptides are selectively recognized and transported toward aggresomes by a CED complex. In: Nature Communications. 2017 ; Vol. 8.
@article{c335698466264dec8d834d9312bac426,
title = "Misfolded polypeptides are selectively recognized and transported toward aggresomes by a CED complex",
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.",
author = "Joori Park and Yeonkyoung Park and Incheol Ryu and Choi, {Mi Hyun} and Lee, {Hyo Jin} and Nara Oh and Kyutae Kim and Kim, {Kyoung Mi} and Junho Choe and Cheolju Lee and Ja-Hyun Baik and Kim, {Yoon Ki}",
year = "2017",
month = "6",
day = "7",
doi = "10.1038/ncomms15730",
language = "English",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Misfolded polypeptides are selectively recognized and transported toward aggresomes by a CED complex

AU - Park, Joori

AU - Park, Yeonkyoung

AU - Ryu, Incheol

AU - Choi, Mi Hyun

AU - Lee, Hyo Jin

AU - Oh, Nara

AU - Kim, Kyutae

AU - Kim, Kyoung Mi

AU - Choe, Junho

AU - Lee, Cheolju

AU - Baik, Ja-Hyun

AU - Kim, Yoon Ki

PY - 2017/6/7

Y1 - 2017/6/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85020664049&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020664049&partnerID=8YFLogxK

U2 - 10.1038/ncomms15730

DO - 10.1038/ncomms15730

M3 - Article

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 15730

ER -