A role for AKT1 in nonsense-mediated mRNA decay.
Martine PalmaCatherine LeroySophie Salomé-DesnoulezElisabeth WerkmeisterRebekah KongMarc MongyHervé Le HirFabrice LejeunePublished in: Nucleic acids research (2021)
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.
Keyphrases
- signaling pathway
- cancer therapy
- protein kinase
- cell proliferation
- quality control
- pi k akt
- drug delivery
- epithelial mesenchymal transition
- induced apoptosis
- transcription factor
- binding protein
- papillary thyroid
- squamous cell carcinoma
- dna methylation
- tyrosine kinase
- amino acid
- small molecule
- young adults
- bioinformatics analysis
- genome wide identification
- childhood cancer