TBC1D7 is the third core subunit of the TSC1-TSC2 complex regulating Rheb/mTORC1.
| Evidence tier | D Mechanistic / in vitro / review |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Mammalian cells |
| Journal | Molecular cell |
| Year | 2012 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/j.molcel.2012.06.009 · PMID 22795129 · Free full text (PMC3693578) |
The tuberous sclerosis complex (TSC) tumor suppressors form the TSC1-TSC2 complex, which limits cell growth in response to poor growth conditions. Through its GTPase-activating protein (GAP) activity toward Rheb, this complex inhibits the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), a key promoter of cell growth. Here, we identify and biochemically characterize TBC1D7 as a stably associated and ubiquitous third core subunit of the TSC1-TSC2 complex. We demonstrate that the TSC1-TSC2-TBC1D7 (TSC-TBC) complex is the functional complex that senses specific cellular growth conditions and possesses Rheb-GAP activity. Sequencing analyses of samples from TSC patients suggest that TBC1D7 is unlikely to represent TSC3. TBC1D7 knockdown decreases the association of TSC1 and TSC2 leading to decreased Rheb-GAP activity, without effects on the localization of TSC2 to the lysosome. Like the other TSC-TBC components, TBC1D7 knockdown results in increased mTORC1 signaling, delayed induction of autophagy, and enhanced cell growth under poor growth conditions.
| Intervention | Biochemical/genetic (TBC1D7) |
| Target | TSC1-TSC2-TBC1D7 / Rheb / mTORC1 |
| Model | Mammalian cells |
| Effect | TBC1D7 is a third subunit of the TSC1-TSC2 complex that regulates Rheb and mTORC1 |