Insulin/IGF1-PI3K-dependent nucleolar localization of a glycolytic enzyme--phosphoglycerate mutase 2, is necessary for proper structure of nucleolus and RNA synthesis
- PMID: 26033454
- PMCID: PMC4627304
- DOI: 10.18632/oncotarget.4044
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.
Keywords: PGAM2; multifunctional enzyme; rRNA; ribosome assembly; squamous cell carcinoma.
Conflict of interest statement
The authors declare no conflict of interest.
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References
-
- Zhang J, Yu L, Fu Q, Gao J, Xie Y, Chen J, Zhang P, Liu Q, Zhao S. Mouse phosphoglycerate mutase M and B isozymes: cDNA cloning, enzyme activity assay and mapping. Gene. 2001;264:273–9. - PubMed
-
- Kowalski W, Nocon D, Gamian A, Kolodziej J, Rakus D. Association of C-terminal region of phosphoglycerate mutase with glycolytic complex regulates energy production in cancer cells. J Cell Physiol. 2012;227:2613–2621. - PubMed
-
- Boisvert FM, van Koningsbruggen S, Navascués J, Lamond AI. The multifunctional nucleolus. Nat Rev Mol Cell Biol. 2007;8:574–585. - PubMed
-
- Takeda K, Komuro Y, Hayakawa T, Oguchi H, Ishida Y, Murakami S, Noguchi T, Kinoshita H, Sekine Y, Iemura S, Natsume T, Ichijo H. Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1. Proc Natl Acad Sci U S A. 2009;106:12301–12305. - PMC - PubMed
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