DEPTOR

The gene DEPTOR can be found only in vertebrates. In human, DEPTOR gene locates at chromosome 8, 8q24.12 with protein size 409 a.a.{{cite web | url = http://useast.ensembl.org/Homo_sapiens/Gene/Family?db=core;g=ENSG00000155792;r=8:119873717-120050913 | title = Homo sapiens - Ensembl protein families - Gene: DEPTOR (ENSG00000155792) | format = | work = Ensembl genome browser 78 }} Human DEPTOR contains two N-terminal DEP domains and a C-terminal PDZ domain.{{cite journal | vauthors = Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, Gray NS, Sabatini DM | title = DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival | journal = Cell | volume = 137 | issue = 5 | pages = 873–86 | date = May 2009 | pmid = 19446321 | doi = 10.1016/j.cell.2009.03.046 | pmc=2758791}}

DEPTOR is involved in mTOR signaling pathway as an endogenous regulator. A direct interaction between DEPTOR and mTOR has been shown. Overexpression of DEPTOR downregulates the activity of mTORC1 and mTORC2 in vitro. mTORC1 and mTORC2 can both inhibit DEPTOR through phosphorylation.

DEPTOR cell-autonomously regulates adipogenesis.{{cite journal | vauthors = Laplante M, Horvat S, Festuccia WT, Birsoy K, Prevorsek Z, Efeyan A, Sabatini DM | title = DEPTOR cell-autonomously promotes adipogenesis, and its expression is associated with obesity | language = English | journal = Cell Metabolism | volume = 16 | issue = 2 | pages = 202–12 | date = Aug 2012 | pmid = 22883231 | pmc = 3463374 | doi = 10.1016/j.cmet.2012.07.008 }} In the muscle, Baf60c promotes a switch from oxidative to glycolytic myofiber type through DEPTOR-mediated Akt/PKB activation.{{cite journal | vauthors = Meng ZX, Li S, Wang L, Ko HJ, Lee Y, Jung DY, Okutsu M, Yan Z, Kim JK, Lin JD | title = Baf60c drives glycolytic metabolism in the muscle and improves systemic glucose homeostasis through Deptor-mediated Akt activation | journal = Nature Medicine | volume = 19 | issue = 5 | pages = 640–5 | date = May 2013 | pmid = 23563706 | pmc = 3650110 | doi = 10.1038/nm.3144 }} Within the brain, DEPTOR is highly expressed in the hippocampus, the medio-basal hypothalamus and the circumventricular organs.{{cite journal | vauthors = Caron A, Baraboi ED, Laplante M, Richard D | title = DEP domain-containing mTOR-interacting protein in the rat brain: distribution of expression and potential implication | language = en | journal = The Journal of Comparative Neurology | volume = 523 | issue = 1 | pages = 93–107 | date = Jan 2015 | pmid = 25159114 | doi = 10.1002/cne.23668 | s2cid = 205683672 | doi-access = free }} Overexpression of DEPTOR in the medio-basal hypothalamus protects mice against high-fat diet-induced obesity by modulating Akt/PKB signaling.{{Cite journal|title = Mediobasal Hypothalamic Overexpression of Deptor Protects Against High-Fat Diet-Induced Obesity|journal = Molecular Metabolism|doi = 10.1016/j.molmet.2015.11.005|pmid = 26909318|pmc = 4735664|first1 = Alexandre|last1 = Caron|first2 = Sébastien M.|last2 = Labbé|first3 = Damien|last3 = Lanfray|first4 = Pierre-Gilles|last4 = Blanchard|first5 = Romain|last5 = Villot|first6 = Christian|last6 = Roy|first7 = David M.|last7 = Sabatini|first8 = Denis|last8 = Richard|first9 = Mathieu|last9 = Laplante|volume=5|issue = 2|pages=102–112|year = 2016}}

Although in most cancer, mTOR pathway is constitutively activated and the expression of DEPTOR is low, one study has found that DEPTOR is overexpressed in multiple myeloma cells and is necessary for their survival.

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