DEP Domain Containing Protein 6 (DEPDC6)

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), AKT, and SGK1, 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), activated AKT. DEPTOR expression was low in most cancers, consistent with activated MTORC1 and MTORC2 pathways. In these cells, high DEPTOR expression was necessary to maintain PI3K and AKT activation, and a reduction in DEPTOR levels resulted in apoptosis.