TY - JOUR
T1 - Multistep regulation of TFEB by MTORC1
AU - Vega-Rubin-de-Celis, Silvia
AU - Peña-Llopis, Samuel
AU - Konda, Meghan
AU - Brugarolas, James
N1 - Publisher Copyright:
© 2017 Taylor & Francis.
PY - 2017/3/4
Y1 - 2017/3/4
N2 - The master regulator of lysosome biogenesis, TFEB, is regulated by MTORC1 through phosphorylation at S211, and a S211A mutation increases nuclear localization. However, TFEBS211A 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.
AB - The master regulator of lysosome biogenesis, TFEB, is regulated by MTORC1 through phosphorylation at S211, and a S211A mutation increases nuclear localization. However, TFEBS211A 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.
KW - Lysosomal biogenesis
KW - MTOR
KW - TFEB
KW - YWHA
KW - subcellular localization
UR - http://www.scopus.com/inward/record.url?scp=85011634328&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011634328&partnerID=8YFLogxK
U2 - 10.1080/15548627.2016.1271514
DO - 10.1080/15548627.2016.1271514
M3 - Article
C2 - 28055300
AN - SCOPUS:85011634328
SN - 1554-8627
VL - 13
SP - 464
EP - 472
JO - Autophagy
JF - Autophagy
IS - 3
ER -