Multistep regulation of TFEB by MTORC1
The master regulator of lysosome biogenesis, TFEB, is regulated by MTORC1 through phosphorylation at S211, and a S211A mutation increases nuclear localization. However, TFEB localizes diffusely in both cytoplasm and nucleus and, as we show, retains regulation by MTORC1. Here, we report that endogeno...
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| Veröffentlicht in: | Autophagy 2017-03, Vol.13 (3), p.464-472 |
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| container_title | Autophagy |
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| creator | Vega-Rubin-de-Celis, Silvia Peña-Llopis, Samuel Konda, Meghan Brugarolas, James |
| description | The master regulator of lysosome biogenesis, TFEB, is regulated by MTORC1 through phosphorylation at S211, and a S211A mutation increases nuclear localization. However, TFEB
localizes diffusely in both cytoplasm and nucleus and, as we show, retains regulation by MTORC1. Here, we report that endogenous TFEB is phosphorylated at S122 in an MTORC1-dependent manner, that S122 is phosphorylated in vitro by recombinant MTOR, and that S122 is important for TFEB regulation by MTORC1. Specifically, nuclear localization following MTORC1 inhibition is blocked by a S122D mutation (despite S211 dephosphorylation). Furthermore, such a mutation inhibits lysosomal biogenesis induced by Torin1. These data reveal a novel mechanism of TFEB regulation by MTORC1 essential for lysosomal biogenesis. |
| doi_str_mv | 10.1080/15548627.2016.1271514 |
| format | Article |
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localizes diffusely in both cytoplasm and nucleus and, as we show, retains regulation by MTORC1. Here, we report that endogenous TFEB is phosphorylated at S122 in an MTORC1-dependent manner, that S122 is phosphorylated in vitro by recombinant MTOR, and that S122 is important for TFEB regulation by MTORC1. Specifically, nuclear localization following MTORC1 inhibition is blocked by a S122D mutation (despite S211 dephosphorylation). Furthermore, such a mutation inhibits lysosomal biogenesis induced by Torin1. These data reveal a novel mechanism of TFEB regulation by MTORC1 essential for lysosomal biogenesis.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>28055300</pmid><doi>10.1080/15548627.2016.1271514</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Basic Brief Reports Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism Cell Nucleus - drug effects Cell Nucleus - metabolism HeLa Cells Humans Lysosomes - drug effects Lysosomes - metabolism Mechanistic Target of Rapamycin Complex 1 - metabolism Mice Models, Biological Naphthyridines - pharmacology Organelle Biogenesis Phosphorylation - drug effects Phosphoserine - metabolism Protein Transport - drug effects |
| title | Multistep regulation of TFEB by MTORC1 |
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