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 2024-01-20T01:31:20Z 2024-01-20T01:31:20Z 2021-09-04 2017-06 2041-1723 https://pubs.kist.re.kr/handle/201004/122697 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. English Nature Publishing Group Misfolded polypeptides are selectively recognized and transported toward aggresomes by a CED complex Article 10.1038/ncomms15730 1 Nature Communications, v.8 Nature Communications 8 Y scie scopus 000402806400001 2-s2.0-85020664049 Multidisciplinary Sciences Science & Technology - Other Topics Article MESSENGER-RNA DECAY PROTEIN-QUALITY CONTROL ELONGATION-FACTOR 1A CAP-BINDING COMPLEX CBP80/20-DEPENDENT TRANSLATION NEURODEGENERATIVE DISEASES CYTOPLASMIC DYNEIN AGGREGATION HISTONE DEGRADATION