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. Author manuscript; available in PMC: 2022 Mar 1.
Published in final edited form as: Free Radic Biol Med. 2021 Jan 29;165:127–136. doi: 10.1016/j.freeradbiomed.2021.01.041

Figure 2. REDD1 acts via TSC2 to suppress mTORC1 by promoting Rheb GTPase activity.

Figure 2.

Two working models have been proposed for the mechanism whereby REDD1 acts to suppress mTORC1. In both models, the suppressive effect of REDD1 on mTORC1 is mediated by a reduction in the proportion of GTP bound to Rheb. In the first model, REDD1 binds 14-3-3 protein to prevent TSC2 sequestration in an inactive complex. In the second, REDD1 promotes dephosphorylation of Akt at Thr308 by PP2A. Akt-dependent phosphorylation of TSC2 suppresses the GAP activity of TSC2 toward Rheb. In addition, REDD1-dependent dephosphorylation of Akt also influences other important targets downstream of Akt, including FOXO transcription factors and GSK3.