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Myc and Omomyc Functionally Associate With the Protein Arginine Methyltransferase 5 (PRMT5) in Glioblastoma Cells

Myc and Omomyc Functionally Associate With the Protein Arginine Methyltransferase 5 (PRMT5) in Glioblastoma Cells

Maria Patrizia Mongiardi, Mauro Savino, Laura Bartoli, Sara Beji, Simona Nanni, Fiorella Scagnoli, Maria Laura Falchetti, Annarita Favia, Antonella Farsetti, Andrea Levi, Sergio Nasi, Barbara Illi

Sci Rep. 2015 Nov 13;5:15494.

PMID: 26563484

Abstract:

The c-Myc protein is dysregulated in many human cancers and its function has not been fully elucitated yet. The c-Myc inhibitor Omomyc displays potent anticancer properties in animal models. It perturbs the c-Myc protein network, impairs c-Myc binding to the E-boxes, retaining transrepressive properties and inducing histone deacetylation. Here we have employed Omomyc to further analyse c-Myc activity at the epigenetic level. We show that both Myc and Omomyc stimulate histone H4 symmetric dimethylation of arginine (R) 3 (H4R3me2s), in human glioblastoma and HEK293T cells. Consistently, both associated with protein Arginine Methyltransferase 5 (PRMT5)--the catalyst of the reaction--and its co-factor Methylosome Protein 50 (MEP50). Confocal experiments showed that Omomyc co-localized with c-Myc, PRMT5 and H4R3me2s-enriched chromatin domains. Finally, interfering with PRMT5 activity impaired target gene activation by Myc whereas it restrained Omomyc-dependent repression. The identification of a histone-modifying complex associated with Omomyc represents the first demonstration of an active role of this miniprotein in modifying chromatin structure and adds new information regarding its action on c-Myc targets. More importantly, the observation that c-Myc may recruit PRMT5-MEP50, inducing H4R3 symmetric di-methylation, suggests previously unpredictable roles for c-Myc in gene expression regulation and new potential targets for therapy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42416085	PRMT5/MEP50 Active human			Price

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