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Protein kinase Cα activation switches YAP1 from TEAD‐mediated signaling to p73‐mediated signaling

Yes‐associated protein 1 (YAP1) interacts with TEAD transcription factor in the nucleus and upregulates TEAD‐target genes. YAP1 is phosphorylated by large tumor suppressor (LATS) kinases, the core kinases of the Hippo pathway, at 5 serine residues and is sequestered and degraded in the cytoplasm. In...

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Autores principales: Sinclear, Caleb Kwame, Maruyama, Junichi, Nagashima, Shunta, Arimoto‐Matsuzaki, Kyoko, Kuleape, Joshua Agbemefa, Iwasa, Hiroaki, Nishina, Hiroshi, Hata, Yutaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990296/
https://www.ncbi.nlm.nih.gov/pubmed/35102644
http://dx.doi.org/10.1111/cas.15285
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author Sinclear, Caleb Kwame
Maruyama, Junichi
Nagashima, Shunta
Arimoto‐Matsuzaki, Kyoko
Kuleape, Joshua Agbemefa
Iwasa, Hiroaki
Nishina, Hiroshi
Hata, Yutaka
author_facet Sinclear, Caleb Kwame
Maruyama, Junichi
Nagashima, Shunta
Arimoto‐Matsuzaki, Kyoko
Kuleape, Joshua Agbemefa
Iwasa, Hiroaki
Nishina, Hiroshi
Hata, Yutaka
author_sort Sinclear, Caleb Kwame
collection PubMed
description Yes‐associated protein 1 (YAP1) interacts with TEAD transcription factor in the nucleus and upregulates TEAD‐target genes. YAP1 is phosphorylated by large tumor suppressor (LATS) kinases, the core kinases of the Hippo pathway, at 5 serine residues and is sequestered and degraded in the cytoplasm. In human cancers with the dysfunction of the Hippo pathway, YAP1 becomes hyperactive and confers malignant properties to cancer cells. We have observed that cold shock induces protein kinase C (PKC)‐mediated phosphorylation of YAP1. PKC phosphorylates YAP1 at 3 serine residues among LATS‐mediate phosphorylation sites. Importantly, PKC activation recruits YAP1 to the cytoplasm even in LATS‐depleted cancer cells and reduces the cooperation with TEAD. PKC activation induces promyelocytic leukemia protein‐mediated SUMOylation of YAP1. SUMOylated YAP1 remains in the nucleus, binds to p73, and promotes p73‐target gene transcription. Bryostatin, a natural anti‐neoplastic reagent that activates PKC, induces YAP1/p73‐mediated apoptosis in cancer cells. Bryostatin reverses malignant transformation caused by the depletion of LATS kinases. Therefore, bryostatin and other reagents that activate PKC are expected to control cancers with the dysfunction of the Hippo pathway.
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spelling pubmed-89902962022-04-13 Protein kinase Cα activation switches YAP1 from TEAD‐mediated signaling to p73‐mediated signaling Sinclear, Caleb Kwame Maruyama, Junichi Nagashima, Shunta Arimoto‐Matsuzaki, Kyoko Kuleape, Joshua Agbemefa Iwasa, Hiroaki Nishina, Hiroshi Hata, Yutaka Cancer Sci ORIGINAL ARTICLES Yes‐associated protein 1 (YAP1) interacts with TEAD transcription factor in the nucleus and upregulates TEAD‐target genes. YAP1 is phosphorylated by large tumor suppressor (LATS) kinases, the core kinases of the Hippo pathway, at 5 serine residues and is sequestered and degraded in the cytoplasm. In human cancers with the dysfunction of the Hippo pathway, YAP1 becomes hyperactive and confers malignant properties to cancer cells. We have observed that cold shock induces protein kinase C (PKC)‐mediated phosphorylation of YAP1. PKC phosphorylates YAP1 at 3 serine residues among LATS‐mediate phosphorylation sites. Importantly, PKC activation recruits YAP1 to the cytoplasm even in LATS‐depleted cancer cells and reduces the cooperation with TEAD. PKC activation induces promyelocytic leukemia protein‐mediated SUMOylation of YAP1. SUMOylated YAP1 remains in the nucleus, binds to p73, and promotes p73‐target gene transcription. Bryostatin, a natural anti‐neoplastic reagent that activates PKC, induces YAP1/p73‐mediated apoptosis in cancer cells. Bryostatin reverses malignant transformation caused by the depletion of LATS kinases. Therefore, bryostatin and other reagents that activate PKC are expected to control cancers with the dysfunction of the Hippo pathway. John Wiley and Sons Inc. 2022-02-17 2022-04 /pmc/articles/PMC8990296/ /pubmed/35102644 http://dx.doi.org/10.1111/cas.15285 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle ORIGINAL ARTICLES
Sinclear, Caleb Kwame
Maruyama, Junichi
Nagashima, Shunta
Arimoto‐Matsuzaki, Kyoko
Kuleape, Joshua Agbemefa
Iwasa, Hiroaki
Nishina, Hiroshi
Hata, Yutaka
Protein kinase Cα activation switches YAP1 from TEAD‐mediated signaling to p73‐mediated signaling
title Protein kinase Cα activation switches YAP1 from TEAD‐mediated signaling to p73‐mediated signaling
title_full Protein kinase Cα activation switches YAP1 from TEAD‐mediated signaling to p73‐mediated signaling
title_fullStr Protein kinase Cα activation switches YAP1 from TEAD‐mediated signaling to p73‐mediated signaling
title_full_unstemmed Protein kinase Cα activation switches YAP1 from TEAD‐mediated signaling to p73‐mediated signaling
title_short Protein kinase Cα activation switches YAP1 from TEAD‐mediated signaling to p73‐mediated signaling
title_sort protein kinase cα activation switches yap1 from tead‐mediated signaling to p73‐mediated signaling
topic ORIGINAL ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990296/
https://www.ncbi.nlm.nih.gov/pubmed/35102644
http://dx.doi.org/10.1111/cas.15285
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