MTOR associated protein LST8 (MLST8)

MTOR associated protein LST8 (MLST8, also known as GbetaL) is a highly conserved WD40 repeat-containing protein and a core component of both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2)[1][5][6]. MLST8 functions chiefly as a molecular scaffold that stabilizes and promotes assembly and catalytic function of the mTOR kinase complexes[1][2][5]. In mTORC2, it serves as a bridge between mTOR and key subunits such as SIN1, enabling complex formation and signal transduction to Akt and other AGC kinases, critical for cell growth, metabolism, and cytoskeletal organization[1][2]. In mTORC1, MLST8 positively regulates mTOR kinase activity, with roles in nutrient and energy sensing, autophagy, and protein synthesis[2][5][6]. Disruption of MLST8 impairs both mTORC1 and especially mTORC2 function, affecting downstream signaling pathways associated with cancer progression and metabolic diseases[3]. MLST8 is not itself a direct drug target, but it is essential for the function of mTOR complexes, which are targeted by approved mTOR inhibitors for cancer and other diseases.

Other names

Target of rapamycin complex subunit LST8G protein beta subunit-likeProtein GbetaLGβLLst8Pop3GableWAT1Mammalian lethal with SEC13 protein 8TORC subunit LST8

Inhibition of mTOR kinase activity (by affecting the mTORC1 and mTORC2 complexes); Disruption of mTORC1/2 assembly or stability (as MLST8 is essential for these complexes)