Fig. 5
From: The physiological mTOR complex 1 inhibitor DDIT4 mediates therapy resistance in glioblastoma
Schematic diagram illustrating DDIT4 effects on mTORC1 signalling and cellular adaptation. Irradiation, alkylating agents and hypoxia induce DDIT4 in glioblastoma cells. DDIT4 relieves 14-3-3-mediated inhibition of the TSC1/2 complex. Active TSC1/2 inhibits Rheb and ultimately mTORC1. This causes a decline in phosphorylation of the mTORC1 targets S6K1, RPS6 and 4E-BP1. An intact DDIT4 sensor effectively inhibits mTORC1 (left panel) and promotes therapy resistance. A defective DDIT4 sensor impairs induction of adaptive programmes prohibiting tumour-protective mTORC1 inhibition (right panel)
