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

胰岛素/IGF1-PI3K 依赖的糖酵解酶——磷酸甘油酸变位酶 2 的核仁定位,对于核仁的正确结构和 RNA 合成是必需的

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

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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