mLST8

mLST8, also known as MLST8 (mammalian lethal with Sec13 protein 8) or GβL, is a conserved WD40-repeat protein that is a core component of the mammalian target of rapamycin (mTOR) signaling pathway. It is the mammalian homolog of yeast LST8 and is found in both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).

mLST8 participates in the assembly and stability of mTORC1 and mTORC2 by interacting with mTOR and their defining subunits RAPTOR (mTORC1) or RICTOR (mTORC2). Although not catalytically active itself, mLST8 acts as a scaffold that influences kinase activity and substrate recruitment. In cells, depletion of MLST8 dampens signaling through both complexes, reducing phosphorylation of mTORC1 substrates S6K1 and 4E-BP1 and of the mTORC2 substrate AKT at serine 473.

mLST8 is broadly expressed and evolutionarily conserved, with its levels and interactions adapting to nutritional and growth cues that regulate mTOR signaling.

Dysregulation of mTOR signaling, in which mLST8 participates, has been linked to cancer and metabolic diseases; targeting the mTOR pathway remains a major therapeutic strategy, though specific inhibitors of MLST8 are not standard clinically.