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@ARTICLE{Minoia:288534,
author = {M. Minoia and J. Quintana-Cordero and K. Jetzinger$^*$ and
I. E. Kotan and K. J. Turnbull and M. Ciccarelli and A. E.
Masser and D. Liebers and E. Gouarin and M. Czech and V.
Hauryliuk and B. Bukau$^*$ and G. Kramer$^*$ and C.
Andréasson},
title = {{C}hp1 is a dedicated chaperone at the ribosome that
safeguards e{EF}1{A} biogenesis.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2024-00398},
pages = {1382},
year = {2024},
note = {DKFZ-ZMBH Alliance},
abstract = {Cotranslational protein folding depends on general
chaperones that engage highly diverse nascent chains at the
ribosomes. Here we discover a dedicated ribosome-associated
chaperone, Chp1, that rewires the cotranslational folding
machinery to assist in the challenging biogenesis of
abundantly expressed eukaryotic translation elongation
factor 1A (eEF1A). Our results indicate that during eEF1A
synthesis, Chp1 is recruited to the ribosome with the help
of the nascent polypeptide-associated complex (NAC), where
it safeguards eEF1A biogenesis. Aberrant eEF1A production in
the absence of Chp1 triggers instant proteolysis, widespread
protein aggregation, activation of Hsf1 stress transcription
and compromises cellular fitness. The expression of
pathogenic eEF1A2 variants linked to epileptic-dyskinetic
encephalopathy is protected by Chp1. Thus, eEF1A is a
difficult-to-fold protein that necessitates a biogenesis
pathway starting with dedicated folding factor Chp1 at the
ribosome to protect the eukaryotic cell from proteostasis
collapse.},
keywords = {Ribosomes: genetics / Ribosomes: metabolism / Protein
Folding / Proteostasis / Eukaryotic Cells: metabolism /
Protein Biosynthesis},
cin = {A250},
ddc = {500},
cid = {I:(DE-He78)A250-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38360885},
pmc = {pmc:PMC10869706},
doi = {10.1038/s41467-024-45645-w},
url = {https://inrepo02.dkfz.de/record/288534},
}