SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation
The Ras family of GTPases are important in cell signaling and frequently mutated in human tumors. Understanding their regulation is thus important for studying biology and human diseases. Here, we report that a novel posttranslational mechanism, reversible lysine fatty acylation, regulates R-Ras2, a...
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doaj-9cb0301a35a7472f8213fc0ba824e33a2021-05-05T13:24:30ZengeLife Sciences Publications LtdeLife2050-084X2017-04-01610.7554/eLife.25158SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylationXiaoyu Zhang0https://orcid.org/0000-0002-0951-9664Nicole A Spiegelman1Ornella D Nelson2Hui Jing3Hening Lin4https://orcid.org/0000-0002-0255-2701Departmeunt of Chemistry and Chemical Biology, Cornell University, Ithaca, United StatesDepartmeunt of Chemistry and Chemical Biology, Cornell University, Ithaca, United StatesDepartmeunt of Chemistry and Chemical Biology, Cornell University, Ithaca, United StatesDepartmeunt of Chemistry and Chemical Biology, Cornell University, Ithaca, United StatesDepartmeunt of Chemistry and Chemical Biology, Cornell University, Ithaca, United States; Howard Hughes Medical Institute, Cornell University, Ithaca, United StatesThe Ras family of GTPases are important in cell signaling and frequently mutated in human tumors. Understanding their regulation is thus important for studying biology and human diseases. Here, we report that a novel posttranslational mechanism, reversible lysine fatty acylation, regulates R-Ras2, a member of the Ras family. SIRT6, a sirtuin with established tumor suppressor function, regulates the lysine fatty acylation of R-Ras2. In mouse embryonic fibroblasts (MEFs), Sirt6 knockout (KO) increased R-Ras2 lysine fatty acylation. Lysine fatty acylation promotes the plasma membrane localization of R-Ras2 and its interaction with phosphatidylinositol 3-kinase PI3K, leading to activated Akt and increased cell proliferation. Our study establishes lysine fatty acylation as a previously unknown mechanism that regulates the Ras family of GTPases and provides an important mechanism by which SIRT6 functions as a tumor suppressor.https://elifesciences.org/articles/25158Rasacylationsirtuindefatty-acylation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaoyu Zhang Nicole A Spiegelman Ornella D Nelson Hui Jing Hening Lin |
spellingShingle |
Xiaoyu Zhang Nicole A Spiegelman Ornella D Nelson Hui Jing Hening Lin SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation eLife Ras acylation sirtuin defatty-acylation |
author_facet |
Xiaoyu Zhang Nicole A Spiegelman Ornella D Nelson Hui Jing Hening Lin |
author_sort |
Xiaoyu Zhang |
title |
SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation |
title_short |
SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation |
title_full |
SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation |
title_fullStr |
SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation |
title_full_unstemmed |
SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation |
title_sort |
sirt6 regulates ras-related protein r-ras2 by lysine defatty-acylation |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2017-04-01 |
description |
The Ras family of GTPases are important in cell signaling and frequently mutated in human tumors. Understanding their regulation is thus important for studying biology and human diseases. Here, we report that a novel posttranslational mechanism, reversible lysine fatty acylation, regulates R-Ras2, a member of the Ras family. SIRT6, a sirtuin with established tumor suppressor function, regulates the lysine fatty acylation of R-Ras2. In mouse embryonic fibroblasts (MEFs), Sirt6 knockout (KO) increased R-Ras2 lysine fatty acylation. Lysine fatty acylation promotes the plasma membrane localization of R-Ras2 and its interaction with phosphatidylinositol 3-kinase PI3K, leading to activated Akt and increased cell proliferation. Our study establishes lysine fatty acylation as a previously unknown mechanism that regulates the Ras family of GTPases and provides an important mechanism by which SIRT6 functions as a tumor suppressor. |
topic |
Ras acylation sirtuin defatty-acylation |
url |
https://elifesciences.org/articles/25158 |
work_keys_str_mv |
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