Fig. 1: Deficiency of Tet2 activates mTORC1 signaling and inhibits autophagy.
From: TET2 is required to suppress mTORC1 signaling through urea cycle with therapeutic potential
a Deficiency of Tet2 increases cell size of mouse liver cells. Left panel, wild-type (Tet2+/+, WT) and Tet2 knockout (Tet2–/–, KO) mice livers were subjected to HE staining. Scale bars, 25 μm. Right panel, cell diameter was calculated by ImageJ. n = 6 biologically independent animals per group. b TET2 KO increases cell size of tumor cells, which can be rescued by rapamycin. Cells were treated with 20 nM rapamycin for 72 h. c TET2 KO increases phosphorylation levels of S6K, S6 and 4EBP1 in tumor cells. d Deficiency of Tet2 leads to increased phosphorylation levels of S6K, S6 and 4Ebp1 in mice livers. n = 6 biologically independent animals per group. e Re-introduction of WT TET2, but not catalytic mutant TET2 (R1896S), can block mTORC1 activation induced by TET2 deficiency. f TET2 KO reduces autophagy in tumor cells, which can be rescued by rapamycin. Cells were treated with 10 nM rapamycin for 24 h. g Tet2 is required for activation of autophagy in mouse livers. Autophagy activation in mouse livers was determined by western blot. n = 6 biologically independent animals per group.
