title: Insulin/IGF1-PI3K-dependent nucleolar localization of a glycolytic enzyme--phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and RNA synthesis.
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.
authors.affiliation: Department of Animal Molecular Physiology, Wroclaw University, Cybulskiego, Wroclaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gizak
authors.affiliation: Department of Animal Molecular Physiology, Wroclaw University, Cybulskiego, Wroclaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Grenda
authors.affiliation: Department of Animal Molecular Physiology, Wroclaw University, Cybulskiego, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Mamczur
authors.affiliation: Department of Animal Molecular Physiology, Wroclaw University, Cybulskiego, Wroclaw, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Wisniewski
authors.affiliation: Department of Biochemistry and Neurobiology, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, Kraków, Poland.
authors.forename: Filip
authors.initials: F
authors.lastname: Sucharski
authors.affiliation: Department of Biochemistry and Neurobiology, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, Kraków, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Silberring
authors.affiliation: Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: McCubrey
authors.affiliation: Biochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry, Martinsried, Germany.
authors.forename: Jacek R
authors.initials: JR
authors.lastname: Wisniewski
authors.affiliation: Department of Animal Molecular Physiology, Wroclaw University, Cybulskiego, Wroclaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Rakus
mesh_terms: D000818:Animals; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D018613:Microscopy, Confocal; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010736:Phosphoglycerate Mutase / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D010736:Phosphoglycerate Mutase
keywords: PGAM2; multifunctional enzyme; rRNA; ribosome assembly; squamous cell carcinoma