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Fine-Tuning of GLI Activity through Arginine Methylation: Its Mechanisms and Function

Department of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
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Cells 2020, 9(9), 1973; https://doi.org/10.3390/cells9091973
Received: 31 July 2020 / Revised: 20 August 2020 / Accepted: 24 August 2020 / Published: 26 August 2020
(This article belongs to the Special Issue Hedgehog Signaling in Development and Cancer)
The glioma-associated oncogene (GLI) family consists of GLI1, GLI2, and GLI3 in mammals. This family has important roles in development and homeostasis. To achieve these roles, the GLI family has widespread outputs. GLI activity is therefore strictly regulated at multiple levels, including via post-translational modifications for context-dependent GLI target gene expression. The protein arginine methyl transferase (PRMT) family is also associated with embryogenesis, homeostasis, and cancer mainly via epigenetic modifications. In the PRMT family, PRMT1, PRMT5, and PRMT7 reportedly regulate GLI1 and GLI2 activity. PRMT1 methylates GLI1 to upregulate its activity and target gene expression. Cytoplasmic PRMT5 methylates GLI1 and promotes GLI1 protein stabilization. Conversely, nucleic PRMT5 interacts with MENIN to suppress growth arrest-specific protein 1 expression, which assists Hedgehog ligand binding to Patched, indirectly resulting in downregulated GLI1 activity. PRMT7-mediated GLI2 methylation upregulates its activity through the dissociation of GLI2 and Suppressor of Fused. Together, PRMT1, PRMT5, and PRMT7 regulate GLI activity at multiple revels. Furthermore, the GLI and PRMT families have strong links with various cancers through cancer stem cell maintenance. Therefore, PRMT-mediated regulation of GLI activity would have important roles in cancer stem cell maintenance. View Full-Text
Keywords: Hedgehog signaling pathway; GLI family; protein arginine methyl transferase; signal transduction; stem cell Hedgehog signaling pathway; GLI family; protein arginine methyl transferase; signal transduction; stem cell
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MDPI and ACS Style

Abe, Y.; Tanaka, N. Fine-Tuning of GLI Activity through Arginine Methylation: Its Mechanisms and Function. Cells 2020, 9, 1973. https://doi.org/10.3390/cells9091973

AMA Style

Abe Y, Tanaka N. Fine-Tuning of GLI Activity through Arginine Methylation: Its Mechanisms and Function. Cells. 2020; 9(9):1973. https://doi.org/10.3390/cells9091973

Chicago/Turabian Style

Abe, Yoshinori, and Nobuyuki Tanaka. 2020. "Fine-Tuning of GLI Activity through Arginine Methylation: Its Mechanisms and Function" Cells 9, no. 9: 1973. https://doi.org/10.3390/cells9091973

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