DEPTOR

Last update 08 May 2025

Basic Info

Synonyms

DEP domain containing MTOR interacting protein, DEP domain-containing mTOR-interacting protein, DEP domain-containing protein 6

+ [4]

Introduction

Negative regulator of the mTORC1 and mTORC2 complexes: inhibits the protein kinase activity of MTOR, thereby inactivating both complexes (PubMed:19446321, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:25936805, PubMed:29382726, PubMed:34519268, PubMed:34519269). DEPTOR inhibits mTORC1 and mTORC2 to induce autophagy (PubMed:22017875, PubMed:22017876, PubMed:22017877). In contrast to AKT1S1/PRAS40, only partially inhibits mTORC1 activity (PubMed:34519268, PubMed:34519269).

100 Clinical Results associated with DEPTOR

100 Translational Medicine associated with DEPTOR

0 Patents (Medical) associated with DEPTOR

264

Literatures (Medical) associated with DEPTOR

01 Dec 2025·Endocrine Pathology

Comprehensive Gene Expression Analysis in Papillary Thyroid Carcinoma Reveals a Transcriptional Profile Associated with Reduced Radioiodine Avidity

Article

Author: Nilsson, Joachim N ; Ihre-Lundgren, Catharina ; Juhlin, C Christofer ; Condello, Vincenzo ; Marchettini, Carlotta

AbstractPapillary thyroid carcinoma (PTC) is the most common form of well-differentiated thyroid cancer (WDTC) and generally has a favorable prognosis. However, subsets of these tumors can metastasize, leading to aggressive disease progression and poorer clinical outcomes. Radioactive iodine (RAI) therapy is routinely given in the adjuvant setting following thyroidectomy and lymph node dissection for WDTC. Nevertheless, its therapeutic efficacy is limited to tumors with high iodine avidity. Early post-surgical classification of thyroid cancers as either iodine-avid or refractory is crucial for enabling more personalized and effective treatment strategies. In this study, we aimed to identify transcriptomic determinants associated with RAI refractoriness (RAI-R) to improve prognostication. We collected clinicopathologic data and conducted RNA-seq on 36 tissue samples (18 high-avidity and 18 low-avidity), each uniquely characterized by ex vivo iodine concentration measurements taken directly from surgical specimens. Whole-transcriptomic analysis identified 63 differentially expressed genes, with six (S100A4, CRTC2, ANO1, WWTR1, DEPTOR, MT1G) showing consistent deregulation. The expression of ANO1, an established iodine transporter at the apical membrane of the thyroid follicular cells, correlated significantly with iodine avidity (r = 0.54). Validation via RT-qPCR confirmed differential expression trends. Gene ontology and pathway enrichment analyses highlighted thyroid hormone synthesis, PI3K-AKT, and MAPK signaling pathways as key regulators of RAI avidity. A refined multivariate predictive model incorporating ANO1 mRNA expression, histological subtypes, and sample type demonstrated strong predictive performance (adjusted R2 = 0.55). These findings suggest ANO1 as a promising biomarker for predicting iodine avidity in thyroid cancer.

01 Apr 2025·Acta Physiologica

Trophoblast‐specific Deptor knockdown enhances trophoblast nutrient transport and fetal growth in mice

Article

Author: Lorca, Ramon ; Urschitz, Johann ; Chicco, Adam J. ; Nunes, Lance G. A. ; Fredrick, Sam Blessen J. ; Atif, Shaikh M. ; Rosario, Fredrick J. ; Weingrill, Rodrigo B. ; Lee, Men‐Jean

AbstractAimSilencing of DEP‐domain containing mTOR‐interacting protein (DEPTOR), an endogenous inhibitor of the mammalian target of rapamycin (mTOR) pathway, increases mTOR signaling and System A/L amino acid transport activity in cultured primary human trophoblast cells. However, there is no evidence supporting the regulatory role of DEPTOR signaling in placental function in vivo. We hypothesized that trophoblast‐specific Deptor knockdown (KD) in mice increases trophoblast mTOR signaling, amino acid transport, and enhances fetal growth.MethodsWe generated trophoblast‐specific DeptorKD transgenic mice, and at embryonic day 18.5, placentas were analyzed to confirm knockdown efficiency, specificity, and mTOR signaling pathway levels. Trophoblast plasma membrane (TPM) System A/L amino acid transport expression and activity were also determined. We also examined the relationship between birthweight and DEPTOR protein levels in human placentas collected at term from appropriate for gestational age (AGA) and large for gestational age (LGA) pregnancies.ResultsReducing trophoblast Deptor RNA levels increased placental mTOR signaling, System A/L transporter expression/activity, and fetal growth in mice. Similarly, human LGA placentas displayed decreased DEPTOR protein levels, inversely correlated to birthweight and BMI.ConclusionsThis is the first report showing that trophoblast‐specific DeptorKD is sufficient to activate mTOR signaling, a master regulator of placental function, which increases the TPM System A and L amino acid transporter expression and activity. We also propose that Deptor expression is mechanistically linked to placental mTOR signaling and fetal growth. Furthermore, modulation of DEPTOR signaling may represent a promising approach to improve outcomes in pregnancies characterized by abnormal fetal growth.

24 Mar 2025·Function

Lentivirus-Mediated Trophoblast-Specific Deptor Knockdown Increases Transplacental System A and System L Amino Acid Transport and Fetal Growth in Mice

Article

Author: Barentsen, Kenneth ; Jansson, Thomas ; Rosario, Fredrick J ; Vaughan, Owen R ; Kramer, Avery ; Powell, Theresa L ; Urschitz, Johann

AbstractMechanistic target of rapamycin (mTOR) signaling is a positive regulator of human placental function including system A/L amino acid transport activity. Placental mTOR signaling is inhibited in fetal growth restriction (FGR) and activated in fetal overgrowth in women; however, the causes of these changes in placental mTOR signaling are unknown. DEP (Dishevelled, Egl-10, Pleckstrin) domain containing mTOR-interacting protein (DEPTOR) is an endogenous inhibitor of mTOR. We tested the hypothesis that trophoblast-specific Deptor knockdown activates placental mTOR signaling and amino acid transport and causes fetal overgrowth. Using lentiviral transduction of blastocyst trophectoderm with a small hairpin RNA, we achieved 47% knockdown of placental Deptor mRNA expression, without altering fetal Deptor mRNA expression. Trophoblast-specific Deptor knockdown activated placental mTORC1 and mTORC2 signaling and increased trophoblast plasma membrane (TPM) LAT1 and SNAT2 protein abundance, and TPM system L and A transporter activity. In addition, Deptor knockdown increased in vivo transplacental system A and L amino acid transport and stimulated placental and fetal growth. In human FGR, placental DEPTOR protein expression was higher and negatively correlated with birth weight and microvillus plasma membrane system A activity. In conclusion, we provide mechanistic evidence that DEPTOR regulates placental mTOR signaling and amino acid transport and fetal growth in vivo. We speculate that modulation of placental DEPTOR is a promising target for intervention in pregnancies characterized by abnormal placental function and fetal growth.

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DEPTOR

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