Alternative titles; symbolsDEP DOMAIN-CONTAINING MTOR-INTERACTING PROTEIN; DEPTORHGNC Approved Gene Symbol: DEPTORCytogenetic location: 8q24.12 Genomic coord...
Alternative titles; symbols
HGNC Approved Gene Symbol: DEPTOR
Cytogenetic location: 8q24.12 Genomic coordinates (GRCh38): 8:119,873,721-120,050,917 (from NCBI)
▼ Cloning and Expression
Peterson et al. (2009) identified DEPDC6, which they called DEPTOR, as a component MTOR (FRAP1; 601231) complexes immunopurified from human embryonic kidney cells, and they obtained the corresponding cDNA. The deduced 409-amino acid protein has 2 DEP domains in its N-terminal half and a PDZ domain near its C terminus. DEPTOR had an apparent molecular mass of 48 kD by SDS-PAGE.
▼ Gene Function
MTOR is a serine/threonine kinase that regulates cell growth and survival via its association with 2 distinct multiprotein complexes, MTORC1 and MTORC2. Using immunoprecipitation analysis, Peterson et al. (2009) found that DEPTOR interacted directly with MTOR, and mutation analysis showed that the FAT domain of MTOR and the PDZ domain of DEPTOR were required for the interaction. Expression of DEPTOR was downregulated by MTORC1 and MTORC2. Loss of DEPTOR activated S6K1 (RPS6KB1; 608938), AKT (see AKT1; 164730), and SGK1 (602958), promoted cell growth and survival, and activated MTORC1 and MTORC2 kinase activities. DEPTOR overexpression suppressed S6K1 but, by relieving feedback inhibition from MTORC1 to PI3 kinase (PI3K; see 601232), activated AKT. Peterson et al. (2009) found that DEPTOR expression was low in most cancers, consistent with activated MTORC1 and MTORC2 pathways. However, DEPTOR was highly overexpressed in a subset of multiple myelomas (254500) harboring cyclin D1 (CCND1; 168461)/cyclin D3 (CCND3; 123834) or MAF (177075)/MAFB (608968) translocations. In these cells, high DEPTOR expression was necessary to maintain PI3K and AKT activation, and a reduction in DEPTOR levels resulted in apoptosis.
Hartz (2009) mapped the DEPDC6 gene to chromosome 8q24.12 based on an alignment of the DEPDC6 sequence (GenBank AK022490) with the genomic sequence (GRCh37).