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Insulin/IGF1-PI3K-dependent nucleolar localization of a glycolytic enzyme – phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and RNA synthesis

Phosphoglycerate mutase (PGAM), a conserved, glycolytic enzyme has been found in nucleoli of cancer cells. Here, we present evidence that accumulation of PGAM in the nucleolus is a universal phenomenon concerning not only neoplastically transformed but also non-malignant cells. Nucleolar localizatio...

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Autores principales: Gizak, Agnieszka, Grenda, Marcin, Mamczur, Piotr, Wisniewski, Janusz, Sucharski, Filip, Silberring, Jerzy, McCubrey, James A., Wisniewski, Jacek R., Rakus, Dariusz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627304/
https://www.ncbi.nlm.nih.gov/pubmed/26033454
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author Gizak, Agnieszka
Grenda, Marcin
Mamczur, Piotr
Wisniewski, Janusz
Sucharski, Filip
Silberring, Jerzy
McCubrey, James A.
Wisniewski, Jacek R.
Rakus, Dariusz
author_facet Gizak, Agnieszka
Grenda, Marcin
Mamczur, Piotr
Wisniewski, Janusz
Sucharski, Filip
Silberring, Jerzy
McCubrey, James A.
Wisniewski, Jacek R.
Rakus, Dariusz
author_sort Gizak, Agnieszka
collection PubMed
description Phosphoglycerate mutase (PGAM), a conserved, glycolytic enzyme has been found in nucleoli of cancer cells. Here, we present evidence that accumulation of PGAM in the nucleolus is a universal phenomenon concerning not only neoplastically transformed but also non-malignant cells. Nucleolar localization of the enzyme is dependent on the presence of the PGAM2 (muscle) subunit and is regulated by insulin/IGF-1–PI3K signaling pathway as well as drugs influencing ribosomal biogenesis. We document that PGAM interacts with several 40S and 60S ribosomal proteins and that silencing of PGAM2 expression results in disturbance of nucleolar structure, inhibition of RNA synthesis and decrease of the mitotic index of squamous cell carcinoma cells. We conclude that presence of PGAM in the nucleolus is a prerequisite for synthesis and initial assembly of new pre-ribosome subunits.
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spelling pubmed-46273042015-12-02 Insulin/IGF1-PI3K-dependent nucleolar localization of a glycolytic enzyme – phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and RNA synthesis Gizak, Agnieszka Grenda, Marcin Mamczur, Piotr Wisniewski, Janusz Sucharski, Filip Silberring, Jerzy McCubrey, James A. Wisniewski, Jacek R. Rakus, Dariusz Oncotarget Research Paper Phosphoglycerate mutase (PGAM), a conserved, glycolytic enzyme has been found in nucleoli of cancer cells. Here, we present evidence that accumulation of PGAM in the nucleolus is a universal phenomenon concerning not only neoplastically transformed but also non-malignant cells. Nucleolar localization of the enzyme is dependent on the presence of the PGAM2 (muscle) subunit and is regulated by insulin/IGF-1–PI3K signaling pathway as well as drugs influencing ribosomal biogenesis. We document that PGAM interacts with several 40S and 60S ribosomal proteins and that silencing of PGAM2 expression results in disturbance of nucleolar structure, inhibition of RNA synthesis and decrease of the mitotic index of squamous cell carcinoma cells. We conclude that presence of PGAM in the nucleolus is a prerequisite for synthesis and initial assembly of new pre-ribosome subunits. Impact Journals LLC 2015-05-08 /pmc/articles/PMC4627304/ /pubmed/26033454 Text en Copyright: © 2015 Gizak et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Gizak, Agnieszka
Grenda, Marcin
Mamczur, Piotr
Wisniewski, Janusz
Sucharski, Filip
Silberring, Jerzy
McCubrey, James A.
Wisniewski, Jacek R.
Rakus, Dariusz
Insulin/IGF1-PI3K-dependent nucleolar localization of a glycolytic enzyme – phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and RNA synthesis
title Insulin/IGF1-PI3K-dependent nucleolar localization of a glycolytic enzyme – phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and RNA synthesis
title_full Insulin/IGF1-PI3K-dependent nucleolar localization of a glycolytic enzyme – phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and RNA synthesis
title_fullStr Insulin/IGF1-PI3K-dependent nucleolar localization of a glycolytic enzyme – phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and RNA synthesis
title_full_unstemmed Insulin/IGF1-PI3K-dependent nucleolar localization of a glycolytic enzyme – phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and RNA synthesis
title_short Insulin/IGF1-PI3K-dependent nucleolar localization of a glycolytic enzyme – phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and RNA synthesis
title_sort insulin/igf1-pi3k-dependent nucleolar localization of a glycolytic enzyme – phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and rna synthesis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627304/
https://www.ncbi.nlm.nih.gov/pubmed/26033454
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