The HSP90/R2TP assembly chaperone promotes cell proliferation in the intestinal epithelium

Chloé Maurizy, Claire Abeza, Bénédicte Lemmers, Monica Gabola, Ciro Longobardi, Valérie Pinet, Marina Ferrand, Conception Paul, Julie Bremond, Francina Langa, François Gerbe, Philippe Jay, Céline Verheggen, Nicola Tinari, Dominique Helmlinger, Rossano Lattanzio, Edouard Bertrand (), Michael Hahne () and Bérengère Pradet-Balade ()
Additional contact information
Chloé Maurizy: CNRS
Claire Abeza: CNRS
Bénédicte Lemmers: CNRS
Monica Gabola: CNRS
Ciro Longobardi: CNRS
Valérie Pinet: CNRS
Marina Ferrand: CNRS
Conception Paul: CNRS
Julie Bremond: CNRS
Francina Langa: Institut Pasteur
François Gerbe: Equipe labélisée Ligue Nationale Contre le Cancer
Philippe Jay: Equipe labélisée Ligue Nationale Contre le Cancer
Céline Verheggen: CNRS
Nicola Tinari: ‘G. d’Annunzio’ University of Chieti–Pescara
Dominique Helmlinger: CNRS
Rossano Lattanzio: ‘G. d’Annunzio’ University of Chieti–Pescara
Edouard Bertrand: CNRS
Michael Hahne: CNRS
Bérengère Pradet-Balade: Equipe labélisée Ligue Nationale Contre le Cancer

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24792-4

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DOI: 10.1038/s41467-021-24792-4

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