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FBXO22 degrades nuclear PTEN to promote tumorigenesis

Nuclear localization of PTEN is essential for its tumor suppressive role, and loss of nuclear PTEN is more prominent than cytoplasmic PTEN in many kinds of cancers. However, nuclear PTEN-specific regulatory mechanisms were rarely reported. Based on the finding that nuclear PTEN is more unstable than...

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Autores principales: Ge, Meng-Kai, Zhang, Na, Xia, Li, Zhang, Cheng, Dong, Shuang-Shu, Li, Zhan-Ming, Ji, Yan, Zheng, Min-Hua, Sun, Jing, Chen, Guo-Qiang, Shen, Shao-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136256/
https://www.ncbi.nlm.nih.gov/pubmed/32249768
http://dx.doi.org/10.1038/s41467-020-15578-1
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author Ge, Meng-Kai
Zhang, Na
Xia, Li
Zhang, Cheng
Dong, Shuang-Shu
Li, Zhan-Ming
Ji, Yan
Zheng, Min-Hua
Sun, Jing
Chen, Guo-Qiang
Shen, Shao-Ming
author_facet Ge, Meng-Kai
Zhang, Na
Xia, Li
Zhang, Cheng
Dong, Shuang-Shu
Li, Zhan-Ming
Ji, Yan
Zheng, Min-Hua
Sun, Jing
Chen, Guo-Qiang
Shen, Shao-Ming
author_sort Ge, Meng-Kai
collection PubMed
description Nuclear localization of PTEN is essential for its tumor suppressive role, and loss of nuclear PTEN is more prominent than cytoplasmic PTEN in many kinds of cancers. However, nuclear PTEN-specific regulatory mechanisms were rarely reported. Based on the finding that nuclear PTEN is more unstable than cytoplasmic PTEN, here we identify that F-box only protein 22 (FBXO22) induces ubiquitylation of nuclear but not cytoplasmic PTEN at lysine 221, which is responsible for the degradation of nuclear PTEN. FBXO22 plays a tumor-promoting role by ubiquitylating and degrading nuclear PTEN. In accordance, FBXO22 is overexpressed in various cancer types, and contributes to nuclear PTEN downregulation in colorectal cancer tissues. Cumulatively, our study reports the mechanism to specifically regulate the stability of nuclear PTEN, which would provide the opportunity for developing therapeutic strategies aiming to achieve complete reactivation of PTEN as a tumor suppressor.
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spelling pubmed-71362562020-04-08 FBXO22 degrades nuclear PTEN to promote tumorigenesis Ge, Meng-Kai Zhang, Na Xia, Li Zhang, Cheng Dong, Shuang-Shu Li, Zhan-Ming Ji, Yan Zheng, Min-Hua Sun, Jing Chen, Guo-Qiang Shen, Shao-Ming Nat Commun Article Nuclear localization of PTEN is essential for its tumor suppressive role, and loss of nuclear PTEN is more prominent than cytoplasmic PTEN in many kinds of cancers. However, nuclear PTEN-specific regulatory mechanisms were rarely reported. Based on the finding that nuclear PTEN is more unstable than cytoplasmic PTEN, here we identify that F-box only protein 22 (FBXO22) induces ubiquitylation of nuclear but not cytoplasmic PTEN at lysine 221, which is responsible for the degradation of nuclear PTEN. FBXO22 plays a tumor-promoting role by ubiquitylating and degrading nuclear PTEN. In accordance, FBXO22 is overexpressed in various cancer types, and contributes to nuclear PTEN downregulation in colorectal cancer tissues. Cumulatively, our study reports the mechanism to specifically regulate the stability of nuclear PTEN, which would provide the opportunity for developing therapeutic strategies aiming to achieve complete reactivation of PTEN as a tumor suppressor. Nature Publishing Group UK 2020-04-06 /pmc/articles/PMC7136256/ /pubmed/32249768 http://dx.doi.org/10.1038/s41467-020-15578-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ge, Meng-Kai
Zhang, Na
Xia, Li
Zhang, Cheng
Dong, Shuang-Shu
Li, Zhan-Ming
Ji, Yan
Zheng, Min-Hua
Sun, Jing
Chen, Guo-Qiang
Shen, Shao-Ming
FBXO22 degrades nuclear PTEN to promote tumorigenesis
title FBXO22 degrades nuclear PTEN to promote tumorigenesis
title_full FBXO22 degrades nuclear PTEN to promote tumorigenesis
title_fullStr FBXO22 degrades nuclear PTEN to promote tumorigenesis
title_full_unstemmed FBXO22 degrades nuclear PTEN to promote tumorigenesis
title_short FBXO22 degrades nuclear PTEN to promote tumorigenesis
title_sort fbxo22 degrades nuclear pten to promote tumorigenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136256/
https://www.ncbi.nlm.nih.gov/pubmed/32249768
http://dx.doi.org/10.1038/s41467-020-15578-1
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