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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http://dx.doi.org/10.18632/oncotarget.4044 | DOI Listing |
Genes (Basel)
December 2024
Faculty of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, Kobe 650-0047, Japan.
Background/objectives: Actin plays a crucial role not only in the cytoplasm, but also in the nucleus, influencing various cellular behaviors, including cell migration and gene expression. Recent studies reveal that nuclear actin dynamics is altered by cellular stresses, such as DNA damage; however, the effect of heat shock on nuclear actin dynamics, particularly in the nucleolus, remains unclear. This study aims to elucidate the contribution of nucleolar actin to cellular responses under heat shock conditions.
View Article and Find Full Text PDFBiomolecules
December 2024
Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain.
CRM1 (XPO1) has been well-characterized as a shuttling receptor that mediates the export of protein and RNA cargos to the cytoplasm, and previous analyses have pinpointed several key residues (A541, F572, K568, S1055, and Q742) that modulate CRM1 export activity. CRM1 also has a less studied nuclear function in RNA biogenesis, which is reflected by its localization to the Cajal body and the nucleolus. Here, we have investigated how the mutation of these key residues affects the intranuclear localization of CRM1 and its ability to mediate export of endogenous cargos.
View Article and Find Full Text PDFIntrinsically disordered arginine-glycine (RG) repeat domains are enriched in multilayered biomolecular condensates such as the nucleolus. nucleolar RG repeats are dispensable for nucleolar accumulation and instead contribute to the organization of sub-nucleolar compartments. The sufficiency of RG repeats to facilitate sub-nucleolar compartmentalization is unclear.
View Article and Find Full Text PDFBiochemistry
January 2025
Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Dimethyladenosine transferase 1 (DIMT1) is an RNA -dimethyladenosine (mA) methyltransferase. DIMT1's role in pre-rRNA processing and ribosome biogenesis is critical for cell proliferation. Here, we investigated the minimal number of residues in a positively charged cleft on DIMT1 required for cell proliferation.
View Article and Find Full Text PDFPhytomedicine
January 2025
Jinan Central Hospital, Shandong First Medical University, Jinan 250013, Shandong, China. Electronic address:
Background: The dysregulation of ribosome biogenesis has been extensively identified in various cancers, making it emerge as a hallmark of malignant cells. This highlights the potential of targeting ribosome biogenesis as an effective approach for treating cancer patients. Although chemotherapy drugs including doxorubicin and cisplatin often target ribosome biogenesis to induce DNA damage or inhibit tumor cell proliferation, they are associated with significant side effects.
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