Targeting mTOR in Glioblastoma: Rationale and Preclinical/Clinical Evidence

Figure 1

(a) mTORC1 protein composition; (b) mTORC1 upstream activators; (c) mTORC1 downstream targets; (d) mTORC1 cellular functions. Legend: DEPTOR: DEP domain TOR-binding protein; mTOR: mechanistic target of rapamycin; RAPTOR: regulatory-associated protein of mTOR; PRAS40: proline-rich AKT substrate 40 kDa; mLST8: mammalian lethal with Sec-13 protein 8; PI3K: phosphatidylinositol-3-kinase; PIP2: phosphatidylinositol (4,5)-bisphosphate; PIP3: phosphatidylinositol (3,4,5)-trisphosphate; PTEN: phosphatase and tensin homolog; AKT: protein kinase B; TSC1/2: tuberous sclerosis complex 1/2; GTP: guanosine triphosphate; RHEB: RAS homolog enriched in brain; FKBP12: 12-kDa intracellular FK506-binding protein; rapalogs: rapamycin analogs; 4EBP1: eukaryotic initiation factor 4E (eIF4E)-binding protein; S6K: ribosomal S6 kinases; GRB10: growth factor receptor-bound protein 10; ULK1/Atg13/FIP200: unc-51-like kinase 1/mammalian autophagy-related gene 13/focal adhesion kinase family-interacting protein of 200 kDa; ATF4: activating transcription factor 4; TFEB: transcription factor EB.

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