Figure 8.

Model for REDD1-dependent regulation of mTORC1 activity and cell growth. Insulin and other growth factors activate mTORC1 through AKT-mediated phosphorylation of TSC2, which promotes TSC2/14–3–3 association and thereby inhibits TSC1/2 function. In response to hypoxia, REDD1 is induced and binds 14–3–3, resulting in TSC2/14–3–3 dissociation, TSC1/2 activation, and mTORC1 inhibition. REDD1 can inhibit mTORC1 even in the presence of constitutive AKT activation. Consequently, loss of REDD1 in this setting induces further mTORC1 activation that drives tumorigenesis.