| Literature DB >> 30886105 |
Jiawen Feng1,2,3, Yaping Dang1,2,3, Weiqi Zhang1,2,3, Xuyang Zhao1,2,3, Cong Zhang1,2,3, Zhiyuan Hou1,2,3, Yan Jin1,2,3, Michael A McNutt1,2,3, Andrew R Marks4,5, Yuxin Yin6,2,3,7.
Abstract
Arginine methylation is a ubiquitous posttranslational modification that regulates critical cellular processes including signal transduction and pre-mRNA splicing. Here, we report that the tumor-suppressor PTEN is methylated by protein arginine methyltransferase 6 (PRMT6). Mass-spectrometry analysis reveals that PTEN is dimethylated at arginine 159 (R159). We found that PTEN is mutated at R159 in cancers, and the PTEN mutant R159K loses its capability to inhibit the PI3K-AKT cascade. Furthermore, PRMT6 is physically associated with PTEN, promotes asymmetrical dimethylation of PTEN, and regulates the PI3K-AKT cascade through PTEN R159 methylation. In addition, using transcriptome analyses, we found that PTEN R159 methylation is involved in modulation of pre-mRNA alternative splicing. Our results demonstrate that PTEN is functionally regulated by arginine methylation. We propose that PTEN arginine methylation modulates pre-mRNA alternative splicing and influences diverse physiologic processes.Entities:
Keywords: PI3K–AKT cascade; PRMT6; PTEN; arginine methylation; pre-mRNA splicing
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Year: 2019 PMID： 30886105 PMCID： PMC6452682 DOI： 10.1073/pnas.1811028116
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205