Article (Scientific journals)
The HSP90/R2TP assembly chaperone promotes cell proliferation in the intestinal epithelium.
Maurizy, Chloé; Abeza, Claire; Lemmers, Bénédicte et al.
2021In Nature Communications, 12 (1), p. 4810
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Keywords :
Animals; Cell Proliferation; Cells, Cultured; Epithelial Cells/cytology/metabolism; HSP90 Heat-Shock Proteins/metabolism; Humans; Intestinal Mucosa/cytology/metabolism; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microscopy, Confocal; Molecular Chaperones/metabolism; Protein Binding; Stem Cells/cytology/metabolism
Abstract :
[en] The R2TP chaperone cooperates with HSP90 to integrate newly synthesized proteins into multi-subunit complexes, yet its role in tissue homeostasis is unknown. Here, we generated conditional, inducible knock-out mice for Rpap3 to inactivate this core component of R2TP in the intestinal epithelium. In adult mice, Rpap3 invalidation caused destruction of the small intestinal epithelium and death within 10 days. Levels of R2TP substrates decreased, with strong effects on mTOR, ATM and ATR. Proliferative stem cells and progenitors deficient for Rpap3 failed to import RNA polymerase II into the nucleus and they induced p53, cell cycle arrest and apoptosis. Post-mitotic, differentiated cells did not display these alterations, suggesting that R2TP clients are preferentially built in actively proliferating cells. In addition, high RPAP3 levels in colorectal tumors from patients correlate with bad prognosis. Here, we show that, in the intestine, the R2TP chaperone plays essential roles in normal and tumoral proliferation.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Maurizy, Chloé  ;  Université de Liège - ULiège > GIGA Stem Cells - Medical Chemistry
Abeza, Claire
Lemmers, Bénédicte
Gabola, Monica
Longobardi, Ciro
Pinet, Valérie
Ferrand, Marina
Paul, Conception
Bremond, Julie
Langa, Francina
Gerbe, François
Jay, Philippe
Verheggen, Céline
Tinari, Nicola
Helmlinger, Dominique
Lattanzio, Rossano
Bertrand, Edouard
Hahne, Michael
Pradet-Balade, Bérengère
More authors (9 more) Less
Language :
English
Title :
The HSP90/R2TP assembly chaperone promotes cell proliferation in the intestinal epithelium.
Publication date :
2021
Journal title :
Nature Communications
eISSN :
2041-1723
Publisher :
Nature Publishing Group, United Kingdom
Volume :
12
Issue :
1
Pages :
4810
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
© 2021. The Author(s).
Available on ORBi :
since 07 September 2021

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