Cited by 845Hippo pathway signaling and YAP/TAZPI3K/AKT/mTOR signaling in cancer14-3-3 protein interactions

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Akt Phosphorylates the Yes-Associated Protein, YAP, to Induce Interaction with 14-3-3 and Attenuation of p73-Mediated Apoptosis

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Basu, Subham, Totty, Nicholas F, Irwin, Meredith S, Sudol, Marius, Downward, Julian·2003·Molecular Cell

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Abstract

We have used an affinity purification method to identify substrates of protein kinase B/Akt. One protein that associates with 14-3-3 in an Akt-dependent manner is shown here to be the Yes-associated protein (YAP), which is phosphorylated by Akt at serine 127, leading to binding to 14-3-3. Akt promotes YAP localization to the cytoplasm, resulting in loss from the nucleus where it functions as a coactivator of transcription factors including p73. p73-mediated induction of Bax expression following DNA damage requires YAP function and is attenuated by Akt phosphorylation of YAP. YAP overexpression increases, while YAP depletion decreases, p73-mediated apoptosis following DNA damage, in an Akt inhibitable manner. Akt phosphorylation of YAP may thus suppress the induction of the proapoptotic gene expression response following cellular damage.

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Authors: Basu, S., Totty, N. F., Irwin, M. S., Sudol, M., & Downward, J.
Affiliations: Cancer Research UK (GB)
Hospital for Sick Children (CA)
Icahn School of Medicine at Mount Sinai (US)
Corresponding author: Downward, Julian
ORCID: Irwin, Meredith S
Sudol, Marius
Downward, Julian
Venue: Molecular Cell
Publisher: Elsevier BV
Published: 2003-01
Volume: 11
Issue: 1
Pages: 11-23
ISSN: 1097-2765 (ISSN-L)
DOI: 10.1016/s1097-2765(02)00776-1
OpenAlex: W2011818472
Cited by: 843
References: 41
Citations by year: 2026: 19 · 2025: 26 · 2024: 41 · 2023: 43 · 2022: 43 · 2021: 51 · 2020: 46 · 2019: 33 · 2018: 47 · 2017: 48 · 2016: 58 · 2015: 41 · 2014: 47 · 2013: 41 · 2012: 26
FWCI: 9.99
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3850 d)
Locations: Molecular Cell (publishedVersion)
PubMed (publishedVersion)
Funders: Cancer Research UK
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
Keywords: Akt, YAP, protein phosphorylation, p73, apoptosis, DNA damage response, Bax expression, nuclear localization, transcriptional coactivation
MeSH terms: Tumor Protein p73, YAP-Signaling Proteins, Animals, Antibodies, Carrier Proteins, Cell Line, DNA-Binding Proteins, Fluorescent Dyes, Humans, Luminescent Proteins, Nuclear Proteins, Phosphoproteins, Phosphorylation, Protein Binding, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Serine, Transcription Factors, Transcription, Genetic, Tyrosine 3-Monooxygenase, Genes, Tumor Suppressor, Apoptosis, Protein Serine-Threonine Kinases, Genes, Reporter, Amino Acid Motifs, Tumor Suppressor Proteins, RNA Interference, Adaptor Proteins, Signal Transducing, 14-3-3 Proteins, Green Fluorescent Proteins, Proto-Oncogene Proteins c-akt

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Akt Phosphorylates the Yes-Associated Protein, YAP, to Induce Interaction with 14-3-3 and Attenuation of p73-Mediated Apoptosis

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