GTP-binding protein Rheb (Rheb)

GTP-binding protein Rheb (Ras homolog enriched in brain) is a small GTPase that serves as a critical molecular switch in the PI3K/Akt/mTOR signaling pathway (UniProt P36544). It functions primarily as a direct and essential activator of the mechanistic target of rapamycin complex 1 (mTORC1), which regulates cell growth, proliferation, and protein synthesis in response to nutrient and energy levels (PubMed: 12740391). Rheb cycles between an active GTP-bound state and an inactive GDP-bound state, a process tightly regulated by the Tuberous Sclerosis Complex (TSC1/TSC2), which acts as a GTPase-activating protein (GAP) (PubMed: 12150925). Mutations in the TSC complex lead to hyperactivation of Rheb, driving diseases such as Tuberous Sclerosis Complex (TSC), lymphangioleiomyomatosis (LAM), and various cancers (PubMed: 24484704). While direct Rheb inhibitors like NR1 are largely in the experimental stage, therapeutic strategies include farnesyltransferase inhibitors like Lonafarnib that prevent Rheb's membrane localization and downstream mTOR inhibitors (PubMed: 28429106).

Other names

Ras homolog enriched in brainRHEB1RHEBRas homolog enriched in brain 1

Inhibition of farnesyltransferase to prevent Rheb membrane localization; direct small-molecule inhibition of GTP binding; indirect inhibition via mTORC1 pathway modulation.