Cargando…
Protein Arginine Methyltransferase 1 Methylates Smurf2
Smurf2, a member of the HECT domain E3 ligase family, is well known for its role as a negative regulator of TGF-β signaling by targeting Smads and TGF-β receptor. However, the regulatory mechanism of Smurf2 has not been elucidated. Arginine methylation is a type of post-translational modification th...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Society for Molecular and Cellular Biology
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546944/ https://www.ncbi.nlm.nih.gov/pubmed/26126536 http://dx.doi.org/10.14348/molcells.2015.0113 |
_version_ | 1782387003533295616 |
---|---|
author | Cha, Boksik Park, Yaerin Hwang, Byul Nim Kim, So-young Jho, Eek-hoon |
author_facet | Cha, Boksik Park, Yaerin Hwang, Byul Nim Kim, So-young Jho, Eek-hoon |
author_sort | Cha, Boksik |
collection | PubMed |
description | Smurf2, a member of the HECT domain E3 ligase family, is well known for its role as a negative regulator of TGF-β signaling by targeting Smads and TGF-β receptor. However, the regulatory mechanism of Smurf2 has not been elucidated. Arginine methylation is a type of post-translational modification that produces monomethylated or dimethylated arginine residues. In this report, we demonstrated methylation of Smurf2 by PRMT1. In vitro methylation assay showed that Smurf2, not Smurf1, was methylated by PRMT1. Among the type I PRMT family, only PRMT1 showed activity for Smurf2. Transiently expressed Smurf2 was methylated by PRMT1, indicating Smurf2 is a novel substrate of PRMT1. Using deletion constructs, methylation sites were shown to be located within amino acid region 224–298 of Smurf2. In vitro methylation assay following point mutation of putative methylation sites confirmed the presence of Arg232, Arg234, Arg237, and Arg239. Knockdown of PRMT1 resulted in increased Smurf2 expression as well as inhibition of TGF-β-mediated reporter activity. Although it is unclear whether or not increased Smurf2 expression can be directly attributed to lack of methylation of arginine residues, our results suggest that methylation by PRMT1 may regulate Smurf2 stability and control TGF-β signaling. |
format | Online Article Text |
id | pubmed-4546944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Korean Society for Molecular and Cellular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-45469442015-09-02 Protein Arginine Methyltransferase 1 Methylates Smurf2 Cha, Boksik Park, Yaerin Hwang, Byul Nim Kim, So-young Jho, Eek-hoon Mol Cells Article Smurf2, a member of the HECT domain E3 ligase family, is well known for its role as a negative regulator of TGF-β signaling by targeting Smads and TGF-β receptor. However, the regulatory mechanism of Smurf2 has not been elucidated. Arginine methylation is a type of post-translational modification that produces monomethylated or dimethylated arginine residues. In this report, we demonstrated methylation of Smurf2 by PRMT1. In vitro methylation assay showed that Smurf2, not Smurf1, was methylated by PRMT1. Among the type I PRMT family, only PRMT1 showed activity for Smurf2. Transiently expressed Smurf2 was methylated by PRMT1, indicating Smurf2 is a novel substrate of PRMT1. Using deletion constructs, methylation sites were shown to be located within amino acid region 224–298 of Smurf2. In vitro methylation assay following point mutation of putative methylation sites confirmed the presence of Arg232, Arg234, Arg237, and Arg239. Knockdown of PRMT1 resulted in increased Smurf2 expression as well as inhibition of TGF-β-mediated reporter activity. Although it is unclear whether or not increased Smurf2 expression can be directly attributed to lack of methylation of arginine residues, our results suggest that methylation by PRMT1 may regulate Smurf2 stability and control TGF-β signaling. Korean Society for Molecular and Cellular Biology 2015-08-31 2015-07-01 /pmc/articles/PMC4546944/ /pubmed/26126536 http://dx.doi.org/10.14348/molcells.2015.0113 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/. |
spellingShingle | Article Cha, Boksik Park, Yaerin Hwang, Byul Nim Kim, So-young Jho, Eek-hoon Protein Arginine Methyltransferase 1 Methylates Smurf2 |
title | Protein Arginine Methyltransferase 1 Methylates Smurf2 |
title_full | Protein Arginine Methyltransferase 1 Methylates Smurf2 |
title_fullStr | Protein Arginine Methyltransferase 1 Methylates Smurf2 |
title_full_unstemmed | Protein Arginine Methyltransferase 1 Methylates Smurf2 |
title_short | Protein Arginine Methyltransferase 1 Methylates Smurf2 |
title_sort | protein arginine methyltransferase 1 methylates smurf2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4546944/ https://www.ncbi.nlm.nih.gov/pubmed/26126536 http://dx.doi.org/10.14348/molcells.2015.0113 |
work_keys_str_mv | AT chaboksik proteinargininemethyltransferase1methylatessmurf2 AT parkyaerin proteinargininemethyltransferase1methylatessmurf2 AT hwangbyulnim proteinargininemethyltransferase1methylatessmurf2 AT kimsoyoung proteinargininemethyltransferase1methylatessmurf2 AT jhoeekhoon proteinargininemethyltransferase1methylatessmurf2 |