DEP domain-containing mTOR-interacting protein (DEPTOR)

DEP domain-containing mTOR-interacting protein (DEPTOR) is a vertebrate-specific regulator of mammalian target of rapamycin (mTOR) complexes, uniquely binding and inhibiting both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2)[1][2][3][4][6]. DEPTOR consists of tandem N-terminal DEP (Dishevelled, Egl-10, Pleckstrin) domains and a C-terminal PDZ (PSD-95, Dlg, ZO-1) domain, responsible for direct interaction with specific surfaces on mTOR[1][2]. Functionally, DEPTOR maintains a feedback loop with mTOR: DEPTOR binding suppresses mTOR activity, but mTOR can also phosphorylate and trigger degradation of DEPTOR, leading to derepression and subsequent activation of mTOR signaling[4][6]. Through its regulation of mTOR, DEPTOR influences cell growth, metabolism, immune homeostasis, and oncogenic or tumor suppressor activities depending on cellular and disease context[1][2][4]. Changes in DEPTOR expression or function are implicated in cancers and metabolic diseases, and the protein’s unique regulatory role is of interest for therapeutic targeting as a modulator of mTOR pathway dynamics[1][2][3][6]. Currently, there are no known drugs that directly target DEPTOR, but modulation of the mTOR-DEPTOR interaction or DEPTOR levels remains an active field of research.

Other names

DEPDC6hDEPTORDEP.6FLJ12428DEP domain-containing protein 6

Inhibition of mTORC1 and mTORC2 kinase activity via direct binding, Negative feedback regulation of mTOR signaling