期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 14, 页码 6868-6877出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1811028116
关键词
PTEN; arginine methylation; PI3K-AKT cascade; pre-mRNA splicing; PRMT6
资金
- National Key Research and Development Program of China [2016YFA0500302]
- National Natural Science Foundation of China [31600618, 81430056, 31420103905, 81372491, 81321003]
- Beijing Natural Science Foundation Key Grant [7161007]
- Peking University Health Science Center Grant [BMU20150503]
- Lam Chung Nin Foundation for Systems Biomedicine at Peking University
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.
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