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

Agnieszka Gizak; Marcin Grenda; Piotr Mamczur; Janusz Wisniewski; Filip Sucharski; Jerzy Silberring; James A. McCubrey; Jacek R. Wisniewski; Dariusz Rakus

doi:10.18632/oncotarget.4044

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Research Papers:

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

Agnieszka Gizak _, Marcin Grenda, Piotr Mamczur, Janusz Wisniewski, Filip Sucharski, Jerzy Silberring, James A. McCubrey, Jacek R. Wisniewski and Dariusz Rakus

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Oncotarget. 2015; 6:17237-17250. https://doi.org/10.18632/oncotarget.4044

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Abstract

Agnieszka Gizak1, Marcin Grenda1, Piotr Mamczur1, Janusz Wisniewski1, Filip Sucharski2, Jerzy Silberring2, James A. McCubrey3, Jacek R. Wisniewski4 and Dariusz Rakus1

1 Department of Animal Molecular Physiology, Wroclaw University, Cybulskiego, Wroclaw, Poland

2 Department of Biochemistry and Neurobiology, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, al. Mickiewicza, Kraków, Poland

3 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, NC, USA

4 Biochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Am Klopferspitz, Martinsried, Germany

Correspondence to:

Agnieszka Gizak, email:

Keywords: squamous cell carcinoma, PGAM2, rRNA, ribosome assembly, multifunctional enzyme

Received: February 25, 2015 Accepted: April 30, 2015 Published: May 08, 2015

Abstract

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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Research Papers:

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

Abstract