MLST8

Description

The MLST8 (MTOR associated protein, LST8 homolog) is a protein-coding gene located on chromosome 16.

MLST8 (MTOR associated protein, LST8 homolog) gene encodes a protein called Target of rapamycin complex subunit LST8, also known as mammalian lethal with SEC13 protein 8 (mLST8), TORC subunit LST8, or G protein beta subunit-like (GβL or Gable). This protein is a subunit of both mTORC1 and mTORC2, complexes that control cell growth and survival in response to nutrient, energy, redox, and hormonal signals. MLST8 is upregulated in several human colon and prostate cancer cell lines and tissues. Knockdown of mLST8 prevents mTORC formation and inhibits tumor growth and invasiveness.

MLST8 is a subunit of both mTORC1 and mTORC2, which are complexes that regulate cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. When nutrients are available, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid, and nucleotide synthesis by phosphorylating substrates such as ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1). Simultaneously, mTORC1 inhibits catabolic pathways by phosphorylating the autophagy initiation components ULK1 and ATG13, as well as the transcription factor TFEB, a master regulator of lysosomal biogenesis and autophagy. The mTORC1 complex is inhibited in response to starvation and amino acid depletion. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, it stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors but appears to be nutrient-insensitive. mTORC2 functions upstream of Rho GTPases to regulate the actin cytoskeleton, possibly by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes serum-induced formation of stress fibers or F-actin. It plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1, a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422' and also modulates the phosphorylation of PRKCA on 'Ser-657'.

MLST8 is also known as GBL, GbetaL, LST8, POP3, WAT1.

Associated Diseases

WES Whole Exome Sequencing