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

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Agnieszka Gizak (Creator)

Marcin Grenda (Creator)

Piotr Mamczur (Creator)

James A. McCubrey (Creator)

Dariusz Rakus (Creator)

Jerzy Silberring (Creator)

Filip Sucharsk (Creator)

Jacek R. Wisniewski (Creator)

Janusz Wisniewski (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Phosphoglycerate mutase (PGAM), a conserved, glycolytic enzyme has been\r\nfound in nucleoli of cancer cells. Here, we present evidence that accumulation of\r\nPGAM in the nucleolus is a universal phenomenon concerning not only neoplastically\r\ntransformed but also non-malignant cells. Nucleolar localization of the enzyme is\r\ndependent on the presence of the PGAM2 (muscle) subunit and is regulated by insulin/\r\nIGF-1–PI3K signaling pathway as well as drugs influencing ribosomal biogenesis. We\r\ndocument that PGAM interacts with several 40S and 60S ribosomal proteins and that\r\nsilencing of PGAM2 expression results in disturbance of nucleolar structure, inhibition\r\nof RNA synthesis and decrease of the mitotic index of squamous cell carcinoma cells.\r\nWe conclude that presence of PGAM in the nucleolus is a prerequisite for synthesis\r\nand initial assembly of new pre-ribosome subunits.

Additional Information

Publication

Other

Language: English

Date: 2023

Subjects

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

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