Affinage

DEPTOR

DEP domain-containing mTOR-interacting protein · UniProt Q8TB45

Length
409 aa
Mass
46.3 kDa
Annotated
2026-06-09
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DEPTOR is an endogenous inhibitory subunit of both mTORC1 and mTORC2 that sets the cellular threshold for mTOR signaling and the PI3K/Akt feedback loop downstream of it (PMID:19446321). It engages mTOR through a bipartite interface: a PDZ domain (with its preceding unstructured linker) binds the mTOR FAT and FRB regions and acts as an anchor, while the N-terminal tandem DEP domains allosterically suppress kinase activation, with mTORC1 reciprocally phosphorylating DEPTOR in a substrate-like mode to relieve inhibition (PMID:34519268, PMID:34519269, PMID:33865870). Loss of DEPTOR activates S6K1, Akt, and SGK1, whereas its accumulation suppresses mTORC1 and, by relieving mTORC1-to-PI3K feedback, can paradoxically activate Akt (PMID:19446321). DEPTOR abundance is governed by a phosphorylation-driven destruction cycle: priming by mTOR followed by CK1α, together with RSK1, S6K1, p38γ/δ and ERK1, generates a phosphodegron recognized by SCF(βTrCP) for ubiquitination and proteasomal degradation, creating a positive feedback loop in which active mTOR destroys its own inhibitor (PMID:22017876, PMID:22017875, PMID:22017877, PMID:26795633, PMID:35216969); APC/C(CDH1) via UBE2C provides an additional degradative input, while OTUB1 and USP-7 (the latter recruited upon ERK1-mediated S235 phosphorylation) deubiquitinate and stabilize DEPTOR (PMID:36548081, PMID:29382726, PMID:35216969). The tandem DEP domains also bind phosphatidic acid, providing a lipid-sensing route for DEPTOR dissociation from mTORC1 (PMID:33865870). Through these activities DEPTOR controls autophagy, adipogenesis, cardiac and mesangial hypertrophy, hepatic fasting metabolism, embryonic stem cell pluripotency, regulatory T cell function, and placental amino acid transport and fetal growth (PMID:26795633, PMID:29940800, PMID:28462079, PMID:25258312, PMID:29969188, PMID:22883231, PMID:40133007). Beyond its mTOR-centered role, DEPTOR also acts as a nuclear DNA-binding transcriptional regulator and engages non-canonical partners including EGFR and ErbB2 (via its PDZ domain), TAZ, and the E3 ligase TRC8 in mTOR-independent functions (PMID:27655709, PMID:34320372, PMID:33995662, PMID:35609371, PMID:32916025). Its expression is set by a wide transcriptional network including NOTCH1, c-Myc, p53, androgen receptor, NF-κB, and the Baf60c-Six4 complex (PMID:27593934, PMID:29666061, PMID:33184290, PMID:26558456, PMID:27179948, PMID:23563706).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2009 High

    Established the founding mechanistic identity of DEPTOR as an mTOR-binding protein that inhibits both mTOR complexes, defining its place in the mTOR/PI3K/Akt signaling axis.

    Evidence Reciprocal Co-IP with mTOR plus RNAi and overexpression read out on S6K1, Akt, and SGK1 phosphorylation

    PMID:19446321

    Open questions at the time
    • Structural basis of inhibition not defined
    • Did not resolve how DEPTOR levels are regulated
  2. 2011 High

    Resolved how DEPTOR levels are controlled, showing growth factor signaling triggers SCF(βTrCP)-mediated degradation through a multi-kinase phosphodegron, creating a feedback loop coupling mTOR activity to destruction of its own inhibitor.

    Evidence In vitro ubiquitination and kinase assays, degron mutagenesis, βTrCP depletion and dominant-negative expression, half-life measurement (three concurrent independent papers; kinases RSK1, S6K1, mTOR priming, CK1α)

    PMID:22017875 PMID:22017876 PMID:22017877

    Open questions at the time
    • Did not address deubiquitinating opposition to degradation
    • In vivo physiological relevance of the loop not yet tested
  3. 2010 Medium

    Linked a pharmacological mTOR inhibitor to DEPTOR, showing resveratrol acts in part by promoting the mTOR-DEPTOR interaction.

    Evidence Co-IP showing enhanced mTOR/DEPTOR association plus RNAi epistasis on leucine-stimulated mTORC1

    PMID:20851890

    Open questions at the time
    • Molecular mechanism by which resveratrol enhances binding unknown
    • Single lab
  4. 2012 Medium

    Defined a physiological output of DEPTOR by showing it is a pro-adipogenic factor that activates the Akt-PPARγ axis through relief of mTORC1 feedback.

    Evidence Transgenic overexpression, siRNA knockdown, adipogenesis and signaling assays with glucocorticoid induction

    PMID:22883231

    Open questions at the time
    • Direct transcriptional partners in adipocytes not defined here
    • Single lab
  5. 2013 Medium

    Connected upstream signaling to DEPTOR abundance in tissue hypertrophy, showing TGF-β/Smad3 and Baf60c-Six4 transcriptionally set DEPTOR levels to tune mTOR output and metabolism.

    Evidence siRNA/overexpression epistasis with mTOR inhibitor in mesangial cells; transgenic muscle model plus ChIP for the Baf60c-Six4 complex on the Deptor promoter

    PMID:23362262 PMID:23563706

    Open questions at the time
    • How multiple transcriptional inputs are integrated unknown
    • Tissue-specific relevance of each input untested
  6. 2014 Medium

    Extended DEPTOR function to stem cell biology, showing it maintains pluripotency by restraining mTOR activity.

    Evidence shRNA knockdown with pluripotency markers and mTORC1 activity during ESC differentiation

    PMID:25258312

    Open questions at the time
    • Mechanism linking mTOR restraint to pluripotency network not defined
    • Single lab
  7. 2016 High

    Identified non-degradative and non-cytoplasmic functions — a p38γ/δ degradation route driving cardiac hypertrophy, and a nuclear DNA-binding transcriptional role sustaining the ER gene network.

    Evidence In vivo p38γ/δ knockout with shRNA rescue of cardiac phenotype; subcellular fractionation and ChIP in myeloma cells

    PMID:26795633 PMID:27655709

    Open questions at the time
    • Nuclear DEPTOR DNA-binding specificity and direct targets incompletely mapped
    • Relationship between nuclear and mTOR-bound pools unknown
  8. 2018 Medium

    Defined the stabilizing arm of DEPTOR turnover and additional protein partners, with OTUB1 and TNFAIP3 stabilizing DEPTOR to control mTORC1, autophagy, and inflammasome activity.

    Evidence In vitro deubiquitination, GST pull-down, Y2H, Co-IP, and confocal microscopy with functional autophagy/inflammasome readouts

    PMID:29382726 PMID:29940800

    Open questions at the time
    • Non-canonical OTUB1 catalytic mechanism on DEPTOR not fully resolved
    • Single lab for each partner
  9. 2021 High

    Delivered the structural mechanism of inhibition: cryo-EM, reconstitution, and crystallography showed a bipartite PDZ-plus-tandem-DEP engagement of mTOR, substrate-like phosphorylation by mTOR, and phosphatidic acid binding by the DEP domains as a dissociation switch.

    Evidence Cryo-EM and in vitro reconstitution of mTORC1 with DEPTOR (two concurrent papers), 1.5 Å crystal structure of tandem DEP domains with lipid-binding assays

    PMID:33865870 PMID:34519268 PMID:34519269

    Open questions at the time
    • Structure of DEPTOR bound within intact mTORC2 not resolved
    • Cellular conditions controlling phosphatidic-acid-driven dissociation untested in vivo
  10. 2021 Medium

    Expanded the regulatory and non-canonical interaction repertoire, identifying SYK/ephrin-driven Tyr289 phosphorylation that weakens mTOR binding, and PDZ-mediated control of EGFR and ErbB2 receptor signaling and stability.

    Evidence Site mutagenesis with BioID; Co-IP with domain mapping, subcellular fractionation, ubiquitination assays, and in vivo Kras;p53 lung tumor models

    PMID:33854045 PMID:33995662 PMID:34320372 PMID:34634301

    Open questions at the time
    • Interplay between receptor-binding and mTOR-inhibitory pools unclear
    • Single lab for each interaction
  11. 2022 Medium

    Mapped the transcriptional network setting DEPTOR levels (NOTCH1, c-Myc, p53, androgen receptor, NF-κB) and defined ERK1-S235 phosphorylation that recruits USP-7 to stabilize DEPTOR, plus a TAZ-binding adipogenic mechanism.

    Evidence ChIP, promoter reporters, and CRISPR binding-site deletion across multiple cancer models; in vitro ERK1 kinase assay with phosphomimetic mutants and USP-7 Co-IP; Co-IP and epistasis for TAZ

    PMID:26558456 PMID:27179948 PMID:27593934 PMID:29666061 PMID:33184290 PMID:35216969 PMID:35609371

    Open questions at the time
    • How competing transcriptional inputs are integrated in a given cell type unknown
    • Each regulatory link rests on a single lab
  12. 2023 High

    Established DEPTOR as the key downstream effector of additional degradation machinery in vivo, with APC/C(CDH1)/UBE2C-driven turnover required for Kras-induced tumorigenesis.

    Evidence Ubiquitination assays plus genetic mouse epistasis (Deptor deletion rescuing Ube2c-loss phenotype in KrasG12D lung tumors)

    PMID:36548081

    Open questions at the time
    • Cell-cycle timing of APC/C-dependent DEPTOR turnover not resolved
    • Relationship to the βTrCP route during tumorigenesis unclear
  13. 2025 Medium

    Demonstrated an organismal physiological role at the maternal-fetal interface, with trophoblast DEPTOR restraining placental mTOR signaling, amino acid transport, and fetal growth, and elevated DEPTOR in human fetal growth restriction.

    Evidence Trophoblast-specific shRNA knockdown in mice with transporter activity and transplacental transport assays, plus human FGR placental correlation (corroborated by concurrent paper)

    PMID:40133007

    Open questions at the time
    • Causal direction of elevated DEPTOR in human FGR not established
    • Upstream signals driving placental DEPTOR levels unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct DEPTOR pools — mTOR-inhibitory, nuclear/transcriptional, and receptor-binding — are partitioned and coordinated within a single cell, and which functions are mTOR-dependent versus independent, remains unresolved.
  • No unified model reconciling cytoplasmic, nuclear, and membrane functions
  • Stoichiometry of DEPTOR within mTORC1 vs mTORC2 in vivo unknown
  • Physiological triggers selecting among degradation and stabilization routes unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0003677 DNA binding 1 GO:0008289 lipid binding 1 GO:0060089 molecular transducer activity 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005634 nucleus 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-9612973 Autophagy 4 R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 1
Partners
BTRCEGFRERBB2MTOROTUB1RNF139USP7WWTR1
Complex memberships
mTORC1mTORC2

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 DEPTOR directly interacts with mTOR and functions as an endogenous inhibitor of both mTORC1 and mTORC2 kinase activities. Loss of DEPTOR activates S6K1, Akt, and SGK1, while DEPTOR overexpression suppresses S6K1 but, by relieving mTORC1-to-PI3K feedback inhibition, activates Akt. Co-immunoprecipitation, RNAi knockdown, overexpression with downstream signaling readouts (S6K1, Akt, SGK1 phosphorylation) Cell High 19446321
2011 DEPTOR is a physiological substrate of SCF(βTrCP) E3 ubiquitin ligase. Upon growth factor stimulation, RSK1 and S6K1 phosphorylate DEPTOR, enabling recognition by βTrCP via its degron sequence, leading to ubiquitination and proteasomal degradation. DEPTOR half-life is shortened by βTrCP and extended by a dominant-negative βTrCP mutant or RSK1/S6K1 inhibition. In vitro ubiquitination assay, co-immunoprecipitation, dominant-negative mutant expression, degron site mutagenesis, half-life measurement Molecular cell High 22017876
2011 mTOR and casein kinase I (CKI) cooperate to phosphorylate DEPTOR, generating a phosphodegron recognized by βTrCP, driving SCF(βTrCP)-dependent proteasomal degradation. This creates a positive feedback loop in which mTOR promotes its own activation by destroying its inhibitor DEPTOR. Phosphorylation assays, co-immunoprecipitation, βTrCP depletion, degron mutation, mTOR inhibitor treatment with signaling readouts Molecular cell High 22017875
2011 DEPTOR is phosphorylated on three serines in a conserved degron by CK1α (after a priming phosphorylation by mTORC1 or mTORC2) in response to mitogens, facilitating binding and ubiquitylation by βTrCP and consequent proteasomal degradation. Blocking this pathway via βTrCP knockdown or a stable DEPTOR mutant unable to bind βTrCP results in mTOR inhibition. Phosphorylation-site mapping, mutagenesis, βTrCP knockdown, stable mutant expression, CK1α involvement established by kinase assays Molecular cell High 22017877
2010 Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR. The inhibitory effect of RSV on leucine-stimulated mTORC1 activation was greatly reduced when DEPTOR was suppressed by RNAi, establishing DEPTOR-dependence of this mechanism. Co-immunoprecipitation, RNAi knockdown, pharmacological treatment with downstream signaling readouts The Journal of biological chemistry Medium 20851890
2021 Cryo-EM and biochemical analysis revealed that both structured regions of DEPTOR — the PDZ domain and the DEP domain tandem (DEPt) — engage mTOR. The PDZ domain binds with a mildly activating effect and acts as an anchor for DEPt, which allosterically suppresses mTOR activation. DEPTOR is itself phosphorylated by mTOR in a substrate-like mode, rationalizing inhibition of non-stimulated mTOR at higher DEPTOR concentrations. Cryo-EM structure determination, biochemical binding assays, domain mutagenesis, kinase assays eLife High 34519268
2021 Reconstitution of mTORC1 with DEPTOR showed DEPTOR is a partial inhibitor of mTORC1. DEPTOR's PDZ domain interacts with the mTOR FAT region and the unstructured linker preceding the PDZ binds the mTOR FRB domain. The linker and PDZ form the minimal inhibitory unit; the N-terminal tandem DEP domains also contribute. mTORC1 activated by RHEB or oncogenic mutation is more potently inhibited by DEPTOR. mTORC1 prevents DEPTOR inhibition by phosphorylating DEPTOR (mutual antagonism). In vitro reconstitution, structural analysis, domain mutagenesis, kinase assays eLife High 34519269
2021 Crystal structure (1.5 Å) of DEPTOR's N-terminal tandem DEP domains shows a dumbbell-shaped structure with an 18-amino-acid DDEX motif at the end of DEP2 that interacts with DEP1 to stabilize the structure. Biochemical studies showed the tandem DEP domains directly interact with phosphatidic acid via two distinct positively charged patches, providing a structural basis for DEPTOR dissociation from mTORC1 upon phosphatidic acid stimulation. X-ray crystallography (1.5 Å resolution), biochemical binding assays with phosphatidic acid Journal of molecular biology High 33865870
2018 OTUB1 directly interacts with DEPTOR via its N-terminal domain and deubiquitinates DEPTOR to stabilize it, in a Cys-91-independent but Asp-88-dependent (non-canonical) manner. The OTUB1-DEPTOR interaction is enhanced by amino acid treatment. OTUB1 suppresses amino acid-induced mTORC1 activation in a DEPTOR-dependent manner, thereby controlling autophagy, cell proliferation, and cell size. Deubiquitination assay, co-immunoprecipitation, domain mutagenesis (Cys-91, Asp-88), siRNA knockdown with signaling readouts The Journal of biological chemistry Medium 29382726
2016 p38γ and p38δ phosphorylate DEPTOR, leading to its degradation and subsequent mTOR activation, thereby promoting cardiac hypertrophy. Hearts from mice lacking p38γ/δ have high DEPTOR levels and low mTOR pathway activity. shRNA-mediated knockdown of Deptor reverted the small-heart phenotype of p38γ/δ knockout mice. In vivo mouse knockout model, shRNA knockdown, cardiomyocyte-specific overexpression, phosphorylation assays, genetic epistasis Nature communications High 26795633
2023 UBE2C couples with APC/C(CDH1) E3 ligase to promote ubiquitylation and degradation of DEPTOR, leading to mTORC signaling activation and promotion of cell cycle progression. KrasG12D-induced UBE2C expression drives DEPTOR degradation; Deptor deletion fully rescued the tumor inhibitory effect of Ube2c deletion in a KrasG12D lung tumor model, establishing DEPTOR as the key downstream effector. Ubiquitination assay, co-immunoprecipitation, genetic mouse models (Ube2c deletion, Deptor deletion, KrasG12D), epistasis rescue experiments The Journal of clinical investigation High 36548081
2016 DEPTOR functions as a nuclear protein in multiple myeloma cells, capable of binding DNA and regulating transcription. Nuclear DEPTOR sustains expression of genes involved in the ER network, and DEPTOR depletion induces ER stress and synergizes with proteasome inhibitor bortezomib. Subcellular fractionation, chromatin immunoprecipitation, siRNA knockdown, ER stress marker analysis Oncotarget Medium 27655709
2015 The ESCRT pathway mediates CXCR4-promoted lysosomal degradation of DEPTOR. CXCR4 stimulates DEPTOR degradation via Gαi and PI3K signaling and via the ESCRT machinery; depletion of ESCRTs by siRNA leads to increased DEPTOR levels and attenuated CXCR4-promoted Akt activation, consistent with decreased mTORC2 activity. siRNA knockdown of ESCRT components, pharmacological inhibition of Gαi and PI3K, western blot for DEPTOR levels and Akt phosphorylation The Journal of biological chemistry Medium 25605718
2013 TGF-β-stimulated Smad3 acts as a key node to suppress DEPTOR abundance, thereby releasing mTORC1/2 inhibition and driving mesangial cell hypertrophy. Sustained (not acute) mTOR activation is required for DEPTOR suppression. Knockdown of Smad3 prevented TGF-β-induced DEPTOR suppression; overexpression of Smad3 decreased DEPTOR; knockdown of DEPTOR reversed Smad7-mediated inhibition of TGF-β-induced hypertrophy. siRNA knockdown, overexpression, mTOR inhibitor (PP242), western blot for DEPTOR levels and mTORC1/2 activity, protein synthesis and cell size assays The Journal of biological chemistry Medium 23362262
2012 GNMT (glycine N-methyltransferase) interacts with DEPTOR/DEPDC6; FRET assay demonstrated that the C-terminal half of GNMT interacts with the PDZ domain of DEPDC6/DEPTOR. Yeast two-hybrid screening, fluorescence resonance energy transfer (FRET) assay, knockdown and overexpression with signaling readouts Molecular medicine Medium 22160218
2013 Baf60c induces expression of DEPTOR via the Baf60c-Six4 transcriptional complex, and DEPTOR then mediates activation of Akt (by relieving mTORC1 negative feedback to PI3K) and glycolytic metabolism in a cell-autonomous manner in skeletal muscle. Transgenic muscle-specific overexpression, ChIP for Baf60c-Six4 binding to Deptor promoter, siRNA knockdown epistasis, metabolic phenotyping in vivo Nature medicine High 23563706
2021 Tyrosine 289 phosphorylation of DEPTOR impairs its interaction with mTOR, leading to increased mTOR activation. SYK (spleen tyrosine kinase) was identified as the kinase responsible for DEPTOR Tyr289 phosphorylation in an ephrin receptor-dependent manner, as established by proximity biotinylation assays and functional validation. Site-directed mutagenesis (Y289), proximity biotinylation (BioID), co-immunoprecipitation, pharmacological inhibition, mTOR signaling readouts The Journal of biological chemistry Medium 34634301
2022 ERK1 phosphorylates DEPTOR at serine 235 (S235), regulating DEPTOR stability. An S235 phosphomimetic DEPTOR mutant was resistant to proteasomal degradation. S235 phosphorylation enables USP-7 deubiquitinase association with DEPTOR; inhibition of USP-7 results in DEPTOR polyubiquitination and degradation. ERK1-mediated S235 phosphorylation of DEPTOR maintains Akt activity in multiple myeloma cells. In vitro kinase assay (ERK1), mutagenesis (S235A and S235D), co-immunoprecipitation for USP-7, proteasome inhibitor rescue, ERK1 knockdown The Journal of biological chemistry Medium 35216969
2016 NOTCH1 directly binds to and activates the human DEPTOR promoter in T-ALL cells, transcriptionally upregulating DEPTOR expression. DEPTOR depletion inhibited Akt activation, abolished cellular proliferation, attenuated glycolytic metabolism, and enhanced cell death in T-ALL cells. Chromatin immunoprecipitation, NOTCH1 overexpression/knockdown with DEPTOR promoter reporter, siRNA knockdown with proliferation/metabolism/apoptosis readouts, xenograft model Oncogene Medium 27593934
2018 DEPTOR directly interacts with c-Myc (via Wnt/β-catenin/c-Myc signaling), and c-Myc binds the DEPTOR promoter to transcriptionally regulate DEPTOR expression in colorectal cancer cells. Inhibition of Wnt/β-catenin or c-Myc knockdown decreased DEPTOR expression; c-Myc overexpression increased it. Chromatin immunoprecipitation (c-Myc binding to DEPTOR promoter), siRNA/shRNA knockdown, luciferase reporter, in vitro and in vivo tumor models Cancer research Medium 29666061
2020 p53 directly binds to the DEPTOR promoter and transactivates DEPTOR expression. Deletion of the p53-binding site on the DEPTOR promoter by CRISPR-Cas9 decreases DEPTOR expression and promotes cell proliferation via Akt signaling. Upon doxorubicin treatment, p53 induces DEPTOR expression leading to cancer cell resistance. Chromatin immunoprecipitation, CRISPR-Cas9 deletion of p53-binding site, luciferase reporter, western blot for downstream signaling Cell death & disease Medium 33184290
2015 Androgen receptor (AR) functions as a negative transcriptional regulator of DEPTOR. DHT treatment repressed DEPTOR mRNA in LNCaP cells in a time-dependent manner, reversed by the AR antagonist bicalutamide. ChIP assay demonstrated AR binds to an AR-responsive element-like region within the 4th intron of the DEPTOR gene, accompanied by reduced acetylated histone H3. RT-PCR, ChIP assay, pharmacological (DHT, bicalutamide), siRNA knockdown with mTORC1 readouts The Journal of toxicological sciences Medium 26558456
2016 p65/NF-κB directly binds the DEPTOR promoter at a -145/-127 region and represses DEPTOR transcription in response to LPS stimulation. Progressive deletions and mutations of the promoter, plus ChIP assays, confirmed this NF-κB binding site is essential for DEPTOR promoter activity. Chromatin immunoprecipitation, promoter deletion/mutation analysis, luciferase reporter, NF-κB inhibitor (PDTC) and IκBα overexpression Gene Medium 27179948
2018 TNFAIP3 (A20) interacts with and stabilizes DEPTOR via its zinc-finger domains; the TNFAIP3-DEPTOR complex rapidly promotes autophagy after LPS treatment to prevent NLRP3 inflammasome formation in monocytes. This interaction was established by GST pull-down, yeast two-hybrid, confocal microscopy, and co-immunoprecipitation. GST pull-down, yeast two-hybrid, co-immunoprecipitation, confocal microscopy, siRNA knockdown with autophagy and inflammasome readouts Autophagy Medium 29940800
2021 DEPTOR directly interacts with ErbB2 at the cell membrane, disrupting ErbB2 polyubiquitination and degradation by β-TrCP. DEPTOR knockdown destabilizes ErbB2, shortens its protein half-life, and inactivates ErbB2-PI3K-AKT-mTOR signaling. A constitutively active ErbB2 mutant fully rescued the reduction in cell proliferation and survival caused by DEPTOR knockdown. Co-immunoprecipitation, immunofluorescence, subcellular fractionation, ubiquitination assay, half-life measurement, constitutively active mutant rescue, siRNA knockdown Theranostics Medium 33995662
2021 Nuclear ErbB2 directly binds to a consensus sequence in the DEPTOR promoter to repress its transcription. ErbB2 kinase activity is required for its nuclear translocation and transcriptional repression of DEPTOR. Repression of DEPTOR by nuclear ErbB2 inhibits autophagy induction by activating mTORC1. Chromatin immunoprecipitation, ErbB2 nuclear translocation experiments (kinase-dead mutant), DEPTOR promoter reporter, autophagy assays Cell death & disease Medium 33854045
2022 DEPTOR binds transcriptional coactivator TAZ and inhibits its transactivation properties, thereby repressing RUNX2 transcriptional activity and elevating PPARγ gene transcription in BMSCs, promoting adipogenesis over osteogenesis. TAZ knockdown in BMSCs abolished the beneficial effects of Deptor ablation on bone-fat balance in mice. Co-immunoprecipitation, TAZ knockdown epistasis, in vivo mouse model of osteoporosis, western blot for RUNX2/PPARγ targets Biomedicine & pharmacotherapy Medium 35609371
2020 DEPTOR interplays with TRC8 E3 ubiquitin ligase in chondrocytes, promoting TRC8 auto-ubiquitination and TRC8 degradation by the ubiquitin-proteasome system. Loss of DEPTOR leads to TRC8 accumulation, excessive ER stress, chondrocyte apoptosis, and osteoarthritis progression, independent of mTOR signaling. Proteomics analysis, co-immunoprecipitation, ubiquitination assay, conditional DEPTOR knockout mice, intra-articular lentivirus injection, ER stress inhibitor rescue Journal of bone and mineral research Medium 32916025
2018 DEPTOR expression in CD4+ T regulatory cells stabilizes Foxp3 expression, shifts metabolism toward oxidative phosphorylation, increases Treg survival and suppressive function. In vivo, induced DEPTOR expression in CD4+ T regulatory cells (not effectors) mediates prolonged cardiac allograft survival in a fully MHC-mismatched transplant model. Conditional knock-in mouse model, in vitro T cell differentiation/metabolism assays, in vivo cardiac allograft transplant model, Foxp3 stability analysis American journal of transplantation Medium 29969188
2017 Liver-specific DEPTOR knockout mice showed sustained mTORC1 activation upon fasting and a reduction in circulating glucose and hepatic glycogen during fasting. Acute rapamycin treatment normalized glycemia, establishing that hepatic DEPTOR accelerates mTORC1 inhibition during the transition to fasting. Loss of DEPTOR also increased oxidative metabolism in hepatocytes, associated with increased cytochrome c expression. Conditional knockout mouse model (Albumin-cre), metabolic phenotyping, rapamycin rescue experiment, hepatocyte oxidative metabolism assays Molecular metabolism Medium 28462079
2014 DEPTOR is a stemness factor that maintains pluripotency in embryonic stem cells by limiting mTOR activity. DEPTOR levels dramatically decrease with ESC differentiation, and knockdown of DEPTOR is sufficient to promote ESC differentiation, accompanied by a corresponding increase in mTORC1 activity. shRNA knockdown, western blot for DEPTOR and mTORC1 activity during differentiation, pluripotency marker analysis The Journal of biological chemistry Medium 25258312
2021 DEPTOR directly binds to the kinase domain of EGFR via its PDZ domain to inactivate EGFR signaling. DEPTOR depletion not only directly activates mTORC1/2 but also relieves EGFR inhibition, further activating mTOR signals and inducing EMT via ZEB1 and SLUG upregulation. In vivo, Deptor deletion accelerated KrasG12D;p53fl/fl-induced lung tumorigenesis via EGFR-mTOR signals. Co-immunoprecipitation (PDZ domain binding to EGFR kinase domain), domain mutagenesis, in vivo KrasG12D;p53fl/fl;Deptor-KO mouse model, signaling readouts Cancer letters Medium 34320372
2019 DEPTOR depletion in prostate cancer cells activates both mTORC1 and mTORC2, induces AKT-dependent EMT, and promotes β-catenin nuclear translocation. In a Deptor-KO mouse model, Deptor knockout accelerated Pten loss-induced prostate tumorigenesis via mTOR signaling activation. Abrogation of mTOR or AKT activation rescued the biological consequences of DEPTOR depletion. Conditional knockout mouse model (Deptor-KO x Pten-loss), siRNA knockdown, pharmacological inhibitors of mTOR and AKT as epistasis tools, migration/invasion assays Oncogene Medium 31685947
2018 RPS27L silencing shortens the protein half-life of β-TrCP (the DEPTOR E3 ligase receptor), leading to DEPTOR accumulation, mTORC1 inactivation, and autophagy induction. Simultaneous DEPTOR silencing partially rescued mTORC1 inactivation and autophagy caused by RPS27L loss, establishing DEPTOR as a causal mediator of this pathway. siRNA knockdown, half-life measurement of β-TrCP, DEPTOR and mTORC1 signaling readouts, double knockdown epistasis Cell death & disease Medium 30425236
2012 DEPTOR is a cell-autonomous pro-adipogenic factor. DEPTOR is induced by glucocorticoids during adipogenesis, and its overexpression promotes while its suppression blocks adipogenesis. DEPTOR activates the proadipogenic Akt/PKB-PPARγ axis by dampening mTORC1-mediated negative feedback inhibition of insulin signaling. Transgenic mouse overexpression model, siRNA knockdown, adipogenesis assays, signaling readouts for Akt/PPARγ, glucocorticoid treatment Cell metabolism Medium 22883231
2025 Trophoblast-specific Deptor knockdown activates placental mTORC1 and mTORC2 signaling, increases trophoblast plasma membrane LAT1 and SNAT2 amino acid transporter expression and activity, and stimulates in vivo transplacental system A and L amino acid transport and fetal growth. In human FGR placentas, DEPTOR protein expression is higher and negatively correlated with birth weight and system A amino acid transporter activity. Lentiviral shRNA trophoblast-specific knockdown in mice, mTOR signaling readouts, transporter expression/activity assays, in vivo transplacental transport measurement Function (Oxford, England) Medium 40133007

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell 978 19446321
2011 DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(βTrCP) E3 ubiquitin ligase and regulates survival and autophagy. Molecular cell 245 22017876
2011 mTOR drives its own activation via SCF(βTrCP)-dependent degradation of the mTOR inhibitor DEPTOR. Molecular cell 216 22017875
2011 mTOR generates an auto-amplification loop by triggering the βTrCP- and CK1α-dependent degradation of DEPTOR. Molecular cell 181 22017877
2010 Resveratrol inhibits mTOR signaling by promoting the interaction between mTOR and DEPTOR. The Journal of biological chemistry 150 20851890
2012 Targeting Cullin-RING ligases by MLN4924 induces autophagy via modulating the HIF1-REDD1-TSC1-mTORC1-DEPTOR axis. Cell death & disease 128 22951983
2013 Baf60c drives glycolytic metabolism in the muscle and improves systemic glucose homeostasis through Deptor-mediated Akt activation. Nature medicine 124 23563706
2012 DEPTOR cell-autonomously promotes adipogenesis, and its expression is associated with obesity. Cell metabolism 97 22883231
2017 Deptor: not only a mTOR inhibitor. Journal of experimental & clinical cancer research : CR 81 28086984
2018 Deptor Is a Novel Target of Wnt/β-Catenin/c-Myc and Contributes to Colorectal Cancer Cell Growth. Cancer research 69 29666061
2018 DEPTOR at the Nexus of Cancer, Metabolism, and Immunity. Physiological reviews 66 29897294
2016 p38γ and δ promote heart hypertrophy by targeting the mTOR-inhibitory protein DEPTOR for degradation. Nature communications 66 26795633
2023 The UBE2C/CDH1/DEPTOR axis is an oncogene and tumor suppressor cascade in lung cancer cells. The Journal of clinical investigation 64 36548081
2012 Targeting the mTOR-DEPTOR pathway by CRL E3 ubiquitin ligases: therapeutic application. Neoplasia (New York, N.Y.) 57 22745582
2018 OTUB1 protein suppresses mTOR complex 1 (mTORC1) activity by deubiquitinating the mTORC1 inhibitor DEPTOR. The Journal of biological chemistry 53 29382726
2012 Functional characterization of glycine N-methyltransferase and its interactive protein DEPDC6/DEPTOR in hepatocellular carcinoma. Molecular medicine (Cambridge, Mass.) 53 22160218
2012 An evolving role for DEPTOR in tumor development and progression. Neoplasia (New York, N.Y.) 53 22745583
2018 DEPTOR regulates osteogenic differentiation via inhibiting MEG3-mediated activation of BMP4 signaling and is involved in osteoporosis. Stem cell research & therapy 50 29973283
2011 Deptor knockdown enhances mTOR Activity and protein synthesis in myocytes and ameliorates disuse muscle atrophy. Molecular medicine (Cambridge, Mass.) 46 21607293
2018 TNFAIP3-DEPTOR complex regulates inflammasome secretion through autophagy in ankylosing spondylitis monocytes. Autophagy 45 29940800
2014 The Baf60c/Deptor pathway links skeletal muscle inflammation to glucose homeostasis in obesity. Diabetes 45 24458360
2015 Deptor enhances triple-negative breast cancer metastasis and chemoresistance through coupling to survivin expression. Neoplasia (New York, N.Y.) 41 25810016
2013 DEPTOR regulates vascular endothelial cell activation and proinflammatory and angiogenic responses. Blood 38 23881914
2019 DEPTOR is an in vivo tumor suppressor that inhibits prostate tumorigenesis via the inactivation of mTORC1/2 signals. Oncogene 37 31685947
2016 DEPTOR is a direct NOTCH1 target that promotes cell proliferation and survival in T-cell leukemia. Oncogene 36 27593934
2016 DEPTOR promotes survival of cervical squamous cell carcinoma cells and its silencing induces apoptosis through downregulating PI3K/AKT and by up-regulating p38 MAP kinase. Oncotarget 33 26992219
2017 Loss of hepatic DEPTOR alters the metabolic transition to fasting. Molecular metabolism 32 28462079
2014 DEPTOR is a stemness factor that regulates pluripotency of embryonic stem cells. The Journal of biological chemistry 32 25258312
2023 PUM1 Promotes Tumor Progression by Activating DEPTOR-Meditated Glycolysis in Gastric Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 31 37469018
2018 Ribosomal protein S27-like regulates autophagy via the β-TrCP-DEPTOR-mTORC1 axis. Cell death & disease 31 30425236
2021 Regulation of human mTOR complexes by DEPTOR. eLife 30 34519268
2015 Mediobasal hypothalamic overexpression of DEPTOR protects against high-fat diet-induced obesity. Molecular metabolism 30 26909318
2013 Transforming growth factor β integrates Smad 3 to mechanistic target of rapamycin complexes to arrest deptor abundance for glomerular mesangial cell hypertrophy. The Journal of biological chemistry 30 23362262
2014 DEPTOR has growth suppression activity against pancreatic cancer cells. Oncotarget 29 25544749
2022 DEPTOR exacerbates bone-fat imbalance in osteoporosis by transcriptionally modulating BMSC differentiation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 35609371
2015 DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells. Biochemical and biophysical research communications 26 25843797
2012 Protective autophagy induced by RBX1/ROC1 knockdown or CRL inactivation via modulating the DEPTOR-MTOR axis. Autophagy 26 22965024
2020 miRNA-182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury. Journal of cellular and molecular medicine 25 32510855
2016 Inhibition of neddylation regulates dendritic cell functions via Deptor accumulation driven mTOR inactivation. Oncotarget 25 27224922
2013 Knockdown of DEPTOR induces apoptosis, increases chemosensitivity to doxorubicin and suppresses autophagy in RPMI-8226 human multiple myeloma cells in vitro. International journal of molecular medicine 25 23503641
2018 Dynamic modelling of the mTOR signalling network reveals complex emergent behaviours conferred by DEPTOR. Scientific reports 24 29330362
2018 DEPTOR Deficiency-Mediated mTORc1 Hyperactivation in Vascular Endothelial Cells Promotes Angiogenesis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 24 29614494
2017 Downregulation of DEPTOR inhibits the proliferation, migration, and survival of osteosarcoma through PI3K/Akt/mTOR pathway. OncoTargets and therapy 24 28932123
2016 Reciprocal Negative Regulation between EGFR and DEPTOR Plays an Important Role in the Progression of Lung Adenocarcinoma. Molecular cancer research : MCR 24 26896556
2015 The endosomal sorting complex required for transport pathway mediates chemokine receptor CXCR4-promoted lysosomal degradation of the mammalian target of rapamycin antagonist DEPTOR. The Journal of biological chemistry 24 25605718
2013 Knockdown of DEPTOR inhibits cell proliferation and increases chemosensitivity to melphalan in human multiple myeloma RPMI-8226 cells via inhibiting PI3K/AKT activity. The Journal of international medical research 24 23613505
2019 Phosphoproteome Analysis Reveals Estrogen-ER Pathway as a Modulator of mTOR Activity Via DEPTOR. Molecular & cellular proteomics : MCP 23 31189691
2012 Placental DEPTOR as a stress sensor during pregnancy. Clinical science (London, England : 1979) 23 21992080
2019 DEPTOR inhibits cell proliferation and confers sensitivity to dopamine agonist in pituitary adenoma. Cancer letters 21 31176743
2017 Argininosuccinate Synthase 1-Deficiency Enhances the Cell Sensitivity to Arginine through Decreased DEPTOR Expression in Endometrial Cancer. Scientific reports 21 28358054
2014 DEPTOR expression negatively correlates with mTORC1 activity and tumor progression in colorectal cancer. Asian Pacific journal of cancer prevention : APJCP 21 24969890
2012 DEPTOR ubiquitination and destruction by SCF(β-TrCP). American journal of physiology. Endocrinology and metabolism 21 22454292
2019 HIF-mediated Suppression of DEPTOR Confers Resistance to mTOR Kinase Inhibition in Renal Cancer. iScience 19 31710966
2016 Cytotoxic Properties of a DEPTOR-mTOR Inhibitor in Multiple Myeloma Cells. Cancer research 19 27530328
2016 Deptor transcriptionally regulates endoplasmic reticulum homeostasis in multiple myeloma cells. Oncotarget 19 27655709
2014 Elucidating the role of DEPTOR in Alzheimer's disease. International journal of molecular medicine 19 25119265
2011 Resveratrol inhibits mTOR signaling by targeting DEPTOR. Communicative & integrative biology 18 21966552
2021 Morin inhibits the transformation of fibroblasts towards myofibroblasts through regulating "PPAR-γ-glutaminolysis-DEPTOR" pathway in pulmonary fibrosis. The Journal of nutritional biochemistry 17 34843935
2018 Loss of DEPTOR in renal tubules protects against cisplatin-induced acute kidney injury. Cell death & disease 17 29670094
2014 DEPTOR is linked to a TORC1-p21 survival proliferation pathway in multiple myeloma cells. Genes & cancer 17 25568666
2021 High glucose-stimulated enhancer of zeste homolog-2 (EZH2) forces suppression of deptor to cause glomerular mesangial cell pathology. Cellular signalling 16 34224844
2021 DEPTOR inhibits lung tumorigenesis by inactivating the EGFR-mTOR signals. Cancer letters 16 34320372
2020 DEPTOR is a direct p53 target that suppresses cell growth and chemosensitivity. Cell death & disease 16 33184290
2018 DEPTOR modulates activation responses in CD4+ T cells and enhances immunoregulation following transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 14 29969188
2017 MNK inversely regulates TELO2 vs. DEPTOR to control mTORC1 signaling. Molecular & cellular oncology 14 28616583
2021 Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells. Cell death & disease 13 33854045
2021 Structural Basis of DEPTOR to Recognize Phosphatidic Acid Using its Tandem DEP Domains. Journal of molecular biology 13 33865870
2021 DEPTOR stabilizes ErbB2 to promote the proliferation and survival of ErbB2-positive breast cancer cells. Theranostics 13 33995662
2020 DEPTOR is a microRNA-155 target regulating migration and cytokine production in diffuse large B-cell lymphoma cells. Experimental hematology 13 32702393
2020 DEPTOR Prevents Osteoarthritis Development Via Interplay With TRC8 to Reduce Endoplasmic Reticulum Stress in Chondrocytes. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 13 32916025
2021 Bipartite binding and partial inhibition links DEPTOR and mTOR in a mutually antagonistic embrace. eLife 12 34519269
2016 DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance. American journal of physiology. Regulatory, integrative and comparative physiology 12 27097662
2024 Deptor protects against myocardial ischemia-reperfusion injury by regulating the mTOR signaling and autophagy. Cell death discovery 11 39702468
2017 Different functions of DEPTOR in modulating sensitivity to chemotherapy for esophageal squamous cell carcinoma. Experimental cell research 11 28267437
2016 Regulator of cullins-1 expression knockdown suppresses the malignant progression of muscle-invasive transitional cell carcinoma by regulating mTOR/DEPTOR pathway. British journal of cancer 11 26742010
2021 Tyrosine phosphorylation of DEPTOR functions as a molecular switch to activate mTOR signaling. The Journal of biological chemistry 10 34634301
2017 DEPTOR-mTOR Signaling Is Critical for Lipid Metabolism and Inflammation Homeostasis of Lymphocytes in Human PBMC Culture. Journal of immunology research 10 28349073
2015 Androgen receptor functions as a negative transcriptional regulator of DEPTOR, mTOR inhibitor. The Journal of toxicological sciences 10 26558456
2021 Design, Synthesis, and Biological Evaluation of Icaritin Derivatives as Novel Putative DEPTOR Inhibitors for Multiple Myeloma Treatment. Journal of medicinal chemistry 9 34644502
2017 Structure-activity relationship study of small molecule inhibitors of the DEPTOR-mTOR interaction. Bioorganic & medicinal chemistry letters 9 28916338
2015 Cul1 promotes melanoma cell proliferation by promoting DEPTOR degradation and enhancing cap-dependent translation. Oncology reports 9 26717892
2020 Metformin attenuates renal interstitial fibrosis through upregulation of Deptor in unilateral ureteral obstruction in rats. Experimental and therapeutic medicine 8 32934682
2019 A Novel Therapeutic Induces DEPTOR Degradation in Multiple Myeloma Cells with Resulting Tumor Cytotoxicity. Molecular cancer therapeutics 8 31395691
2016 Chemopreventive Effect of Dietary Glutamineon Colitis-Associated Colorectal Cancer Is Associated with Modulation of the DEPTOR/mTOR Signaling Pathway. Nutrients 8 27144580
2020 Regulatory role of DEPTOR‑mediated cellular autophagy and mitochondrial reactive oxygen species in angiogenesis in multiple myeloma. International journal of molecular medicine 7 33416146
2022 Turnover of the mTOR inhibitor, DEPTOR, and downstream AKT phosphorylation in multiple myeloma cells, is dependent on ERK1-mediated phosphorylation. The Journal of biological chemistry 6 35216969
2022 Stabilization of DEPTOR sensitizes hypopharyngeal cancer to radiotherapy via targeting degradation. Molecular therapy oncolytics 6 36090478
2021 Downregulation of miR-96-5p Inhibits mTOR/NF-κb Signaling Pathway via DEPTOR in Allergic Rhinitis. International archives of allergy and immunology 6 33477144
2016 p65 down-regulates DEPTOR expression in response to LPS stimulation in hepatocytes. Gene 6 27179948
2025 Trophoblast-specific Deptor knockdown enhances trophoblast nutrient transport and fetal growth in mice. Acta physiologica (Oxford, England) 5 40042094
2024 miR-193b-5p promotes GCRV replication by inhibiting autophagy via targeting deptor in grass carp (Ctenopharyngodon idellus). Fish & shellfish immunology 5 38365163
2021 Function of Deptor and its roles in hematological malignancies. Aging 5 33412518
2016 DEPTOR promoter genetic variants and insulin resistance in obese children and adolescents. Pediatric diabetes 5 26871578
2025 Lentivirus-Mediated Trophoblast-Specific Deptor Knockdown Increases Transplacental System A and System L Amino Acid Transport and Fetal Growth in Mice. Function (Oxford, England) 4 40133007
2024 DEPTOR attenuates asthma progression by suppressing endoplasmic reticulum stress through SOD1. Biology direct 4 39533404
2022 DFNA5 inhibits colorectal cancer proliferation by suppressing the mTORC1/2 signaling pathways via upregulation of DEPTOR. Cell cycle (Georgetown, Tex.) 4 35923131
2022 DEPTOR loss impairs brown adipocyte development in vitro but has limited impacts in mice. Molecular metabolism 4 36535626
2021 DEPTOR in Skeletal Development and Diseases. Frontiers in genetics 4 34122519
2021 Exploring novel and potent molecules for disrupting DEPTOR-mTOR interaction through structure-steered screening, extra-exactitude molecular docking, prime binding free energy estimation and voguish molecular dynamics. Journal of biomolecular structure & dynamics 4 34431457
2020 [MicroRNA-671-3p suppresses proliferation and invasion of breast cancer cells by targeting DEPTOR]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 4 32376551

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