regulation of extrinsic apoptotic signaling pathway / negative regulation of TORC2 signaling / phosphatidic acid binding / negative regulation of cell size / negative regulation of TOR signaling / protein serine/threonine kinase inhibitor activity / protein kinase inhibitor activity / negative regulation of TORC1 signaling / positive regulation of autophagy / GTPase activator activity ...regulation of extrinsic apoptotic signaling pathway / negative regulation of TORC2 signaling / phosphatidic acid binding / negative regulation of cell size / negative regulation of TOR signaling / protein serine/threonine kinase inhibitor activity / protein kinase inhibitor activity / negative regulation of TORC1 signaling / positive regulation of autophagy / GTPase activator activity / guanyl-nucleotide exchange factor activity / negative regulation of protein kinase activity / intracellular signal transduction / G protein-coupled receptor signaling pathway / lysosomal membrane / plasma membrane 類似検索 - 分子機能
DEP domain-containing mTOR-interacting protein, DEP domain 1 / DEP domain-containing mTOR-interacting protein, DEP domain 2 / : / Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP) / DEP domain profile. / Domain found in Dishevelled, Egl-10, and Pleckstrin / DEP domain / PDZ domain profile. / Domain present in PSD-95, Dlg, and ZO-1/2. / PDZ domain ...DEP domain-containing mTOR-interacting protein, DEP domain 1 / DEP domain-containing mTOR-interacting protein, DEP domain 2 / : / Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP) / DEP domain profile. / Domain found in Dishevelled, Egl-10, and Pleckstrin / DEP domain / PDZ domain profile. / Domain present in PSD-95, Dlg, and ZO-1/2. / PDZ domain / PDZ superfamily / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily 類似検索 - ドメイン・相同性
DEP domain-containing mTOR-interacting protein 類似検索 - 構成要素
ジャーナル: Elife / 年: 2021 タイトル: Regulation of human mTOR complexes by DEPTOR. 著者: Matthias Wälchli / Karolin Berneiser / Francesca Mangia / Stefan Imseng / Louise-Marie Craigie / Edward Stuttfeld / Michael N Hall / Timm Maier / 要旨: The vertebrate-specific DEP domain-containing mTOR interacting protein (DEPTOR), an oncoprotein or tumor suppressor, has important roles in metabolism, immunity, and cancer. It is the only protein ...The vertebrate-specific DEP domain-containing mTOR interacting protein (DEPTOR), an oncoprotein or tumor suppressor, has important roles in metabolism, immunity, and cancer. It is the only protein that binds and regulates both complexes of mammalian target of rapamycin (mTOR), a central regulator of cell growth. Biochemical analysis and cryo-EM reconstructions of DEPTOR bound to human mTOR complex 1 (mTORC1) and mTORC2 reveal that both structured regions of DEPTOR, the PDZ domain and the DEP domain tandem (DEPt), are involved in mTOR interaction. The PDZ domain binds tightly with mildly activating effect, but then acts as an anchor for DEPt association that allosterically suppresses mTOR activation. The binding interfaces of the PDZ domain and DEPt also support further regulation by other signaling pathways. A separate, substrate-like mode of interaction for DEPTOR phosphorylation by mTOR complexes rationalizes inhibition of non-stimulated mTOR activity at higher DEPTOR concentrations. The multifaceted interplay between DEPTOR and mTOR provides a basis for understanding the divergent roles of DEPTOR in physiology and opens new routes for targeting the mTOR-DEPTOR interaction in disease.