Tuberous sclerosis 2 protein (TSC2) (TSC2)

Tuberin is a critical tumor suppressor protein encoded by the TSC2 gene that plays a central role in the regulation of cell growth and proliferation [1, 2]. It functions as part of a heterodimeric complex with hamartin (TSC1) to act as a GTPase-activating protein (GAP) for the small GTPase Rheb [1]. By stimulating the conversion of Rheb-GTP to Rheb-GDP, tuberin effectively inhibits the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, which is a master regulator of protein synthesis and cell metabolism [1, 3]. Loss-of-function mutations in the TSC2 gene lead to constitutive activation of mTORC1, resulting in the development of Tuberous Sclerosis Complex (TSC), a multi-system genetic disorder characterized by the growth of benign tumors in various organs [3, 4]. It is also implicated in Lymphangioleiomyomatosis (LAM), a rare lung disease [3]. Therapeutic strategies for TSC2-related pathologies primarily involve the use of mTOR inhibitors, such as sirolimus and everolimus, which compensate for the loss of tuberin's inhibitory function [3]. These drugs help manage symptoms like subependymal giant cell astrocytomas and renal angiomyolipomas by reducing mTORC1 activity [4].

Other names

TuberinTSC2PPP1R160Tuberous sclerosis 2 protein

mTORC1 inhibition