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Prmt5 Activates Akt Via Methylation To Promote Tumor Metastasis., Lei Huang, Xiao-Ou Zhang, Esteban J Rozen, Xiaomei Sun, Benjamin Sallis, Odette Verdejo-Torres, Kim Wigglesworth, Daniel Moon, Tingting Huang, John P Cavaretta, Gang Wang, Lei Zhang, Jason M Shohet, Mary M. Lee, Qiong Wu

Department of Pediatrics Faculty Papers

Protein arginine methyltransferase 5 (PRMT5) is the primary methyltransferase generating symmetric-dimethyl-arginine marks on histone and non-histone proteins. PRMT5 dysregulation is implicated in multiple oncogenic processes. Here, we report that PRMT5-mediated methylation of protein kinase B (AKT) is required for its subsequent phosphorylation at Thr308 and Ser473. Moreover, pharmacologic or genetic inhibition of PRMT5 abolishes AKT1 arginine 15 methylation, thereby preventing AKT1 translocation to the plasma membrane and subsequent recruitment of its upstream activating kinases PDK1 and mTOR2. We show that PRMT5/AKT signaling controls the expression of the epithelial-mesenchymal-transition transcription factors ZEB1, SNAIL, and TWIST1. PRMT5 inhibition significantly attenuates primary tumor …