Nakatsumi Hirokazu, Oka Takeru, Higa Tsunaki, Shirane Michiko, Nakayama Keiichi I
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
Genes Cells. 2018 Jul;23(7):599-605. doi: 10.1111/gtc.12597. Epub 2018 May 29.
Mammalian target of rapamycin complex 1 (mTORC1) kinase is a master regulator of the cellular response to nutrition-related signals such as insulin and amino acids. mTORC1 is activated on the lysosomal membrane and induces phosphorylation of a variety of downstream molecules. We previously showed that activated mTORC1 induces protein phosphatase 2A (PP2A)-mediated dephosphorylation of the transcription factor forkhead box K1 (FOXK1). The mechanism underlying the signal transduction from the cytoplasmic mTORC1 to the nuclear FOXK1 has remained unclear, however, we now show that a nuclear-cytoplasmic transport system is necessary for the mTORC1-FOXK1 signal transduction. This reaction is mediated by a shuttling protein B56, which is a regulatory subunit of PP2A and plays an essential role in the mTORC1-dependent dephosphorylation of FOXK1. These results suggest that PP2A phosphatase contributes to the signaling for mTORC1-dependent transcriptional regulation.
雷帕霉素靶蛋白复合物1（mTORC1）激酶是细胞对胰岛素和氨基酸等营养相关信号作出反应的主要调节因子。mTORC1在溶酶体膜上被激活，并诱导多种下游分子的磷酸化。我们之前表明，激活的mTORC1会诱导蛋白磷酸酶2A（PP2A）介导的转录因子叉头框K1（FOXK1）去磷酸化。然而，从细胞质mTORC1到细胞核FOXK1的信号转导机制仍不清楚，现在我们表明，核质转运系统对于mTORC1-FOXK1信号转导是必需的。该反应由穿梭蛋白B56介导，B56是PP2A的调节亚基，在mTORC1依赖的FOXK1去磷酸化中起关键作用。这些结果表明，PP2A磷酸酶有助于mTORC1依赖的转录调控信号传导。
