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PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription
PTEN is a critical tumour suppressor that is frequently mutated in human cancer. We have previously identified a CUG initiated PTEN isoform designated PTENα, which functions in mitochondrial bioenergetics. Here we report the identification of another N-terminal extended PTEN isoform, designated PTEN...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376652/ https://www.ncbi.nlm.nih.gov/pubmed/28332494 http://dx.doi.org/10.1038/ncomms14771 |
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author | Liang, Hui Chen, Xi Yin, Qi Ruan, Danhui Zhao, Xuyang Zhang, Cong McNutt, Michael A. Yin, Yuxin |
author_facet | Liang, Hui Chen, Xi Yin, Qi Ruan, Danhui Zhao, Xuyang Zhang, Cong McNutt, Michael A. Yin, Yuxin |
author_sort | Liang, Hui |
collection | PubMed |
description | PTEN is a critical tumour suppressor that is frequently mutated in human cancer. We have previously identified a CUG initiated PTEN isoform designated PTENα, which functions in mitochondrial bioenergetics. Here we report the identification of another N-terminal extended PTEN isoform, designated PTENβ. PTENβ translation is initiated from an AUU codon upstream of and in-frame with the AUG initiation sequence for canonical PTEN. We show that the Kozak context and a downstream hairpin structure are critical for this alternative initiation. PTENβ localizes predominantly in the nucleolus, and physically associates with and dephosphorylates nucleolin, which is a multifunctional nucleolar phosphoprotein. Disruption of PTENβ alters rDNA transcription and promotes ribosomal biogenesis, and this effect can be reversed by re-introduction of PTENβ. Our data show that PTENβ regulates pre-rRNA synthesis and cellular proliferation. These results demonstrate the complexity of the PTEN protein family and the diversity of its functions. |
format | Online Article Text |
id | pubmed-5376652 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53766522017-04-17 PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription Liang, Hui Chen, Xi Yin, Qi Ruan, Danhui Zhao, Xuyang Zhang, Cong McNutt, Michael A. Yin, Yuxin Nat Commun Article PTEN is a critical tumour suppressor that is frequently mutated in human cancer. We have previously identified a CUG initiated PTEN isoform designated PTENα, which functions in mitochondrial bioenergetics. Here we report the identification of another N-terminal extended PTEN isoform, designated PTENβ. PTENβ translation is initiated from an AUU codon upstream of and in-frame with the AUG initiation sequence for canonical PTEN. We show that the Kozak context and a downstream hairpin structure are critical for this alternative initiation. PTENβ localizes predominantly in the nucleolus, and physically associates with and dephosphorylates nucleolin, which is a multifunctional nucleolar phosphoprotein. Disruption of PTENβ alters rDNA transcription and promotes ribosomal biogenesis, and this effect can be reversed by re-introduction of PTENβ. Our data show that PTENβ regulates pre-rRNA synthesis and cellular proliferation. These results demonstrate the complexity of the PTEN protein family and the diversity of its functions. Nature Publishing Group 2017-03-23 /pmc/articles/PMC5376652/ /pubmed/28332494 http://dx.doi.org/10.1038/ncomms14771 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Liang, Hui Chen, Xi Yin, Qi Ruan, Danhui Zhao, Xuyang Zhang, Cong McNutt, Michael A. Yin, Yuxin PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription |
title | PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription |
title_full | PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription |
title_fullStr | PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription |
title_full_unstemmed | PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription |
title_short | PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription |
title_sort | ptenβ is an alternatively translated isoform of pten that regulates rdna transcription |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376652/ https://www.ncbi.nlm.nih.gov/pubmed/28332494 http://dx.doi.org/10.1038/ncomms14771 |
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