Journal
NUCLEIC ACIDS RESEARCH
Volume 49, Issue 19, Pages 11022-11037Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkab882
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Funding
- La Ligue contre le Cancer
- Vaincre la mucoviscidose
- Association Francaise contre les Myopathies
- GIP Canceropole Nord Ouest
- University of Lille
- la Region Hauts-de-France
- Contrat de Plan Etat-Region CPER Cancer 2015-2020
- CNRS institution
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Nonsense-mediated mRNA decay (NMD) is a highly regulated quality control mechanism that degrades mRNAs containing premature termination codons. AKT1 kinase plays a crucial role in NMD by phosphorylating UPF1, which may have implications in cancer processes and therapy due to its overactivation in cancer cells.
Nonsense-mediated mRNA decay (NMD) is a highly regulated quality control mechanism through which mRNAs harboring a premature termination codon are degraded. It is also a regulatory pathway for some genes. This mechanism is subject to various levels of regulation, including phosphorylation. To date only one kinase, SMG1, has been described to participate in NMD, by targeting the central NMD factor UPF1. Here, screening of a kinase inhibitor library revealed as putative NMD inhibitors several molecules targeting the protein kinase AKT1. We present evidence demonstrating that AKT1, a central player in the PI3K/AKT/mTOR signaling pathway, plays an essential role in NMD, being recruited by the UPF3X protein to phosphorylate UPF1. As AKT1 is often overactivated in cancer cells and as this should result in increased NMD efficiency, the possibility that this increase might affect cancer processes and be targeted in cancer therapy is discussed.
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