mTORC1 directly phosphorylates and regulates human MAF1.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_EA2B2962787E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
mTORC1 directly phosphorylates and regulates human MAF1.
Périodique
Molecular and cellular biology
Auteur(s)
Michels A.A., Robitaille A.M., Buczynski-Ruchonnet D., Hodroj W., Reina J.H., Hall M.N., Hernandez N.
ISSN
1098-5549 (Electronic)
ISSN-L
0270-7306
Statut éditorial
Publié
Date de publication
08/2010
Peer-reviewed
Oui
Volume
30
Numéro
15
Pages
3749-3757
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1.

Mots-clé
Humans, Phosphorylation, RNA Polymerase III/antagonists & inhibitors, RNA Polymerase III/genetics, RNA Polymerase III/metabolism, Signal Transduction/drug effects, Signal Transduction/genetics, Sirolimus/metabolism, Sirolimus/pharmacology, Transfection
Pubmed
Web of science
Open Access
Oui
Création de la notice
10/06/2010 14:53
Dernière modification de la notice
20/08/2019 17:12
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