DEP domain-containing mTOR-interacting protein (DEPTOR) also known as DEP domain-containing protein 6 (DEPDC6) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''DEPTOR''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Structure
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.
Human DEPTOR contains two
N-terminal DEP domain
In molecular biology, the DEP domain (Dishevelled, Egl-10 and Pleckstrin domain) is a globular protein domain of about 80 amino acids that is found in over 50 proteins involved in G-protein signalling pathways. It was named after the three protei ...
s and a
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
PDZ domain
The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals. Proteins containing PDZ domains play a key role in anchoring receptor proteins in the membrane to ...
.
Function
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
mTORC1, also known as mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1, is a protein complex that functions as a nutrient/energy/redox sensor and controls protein synthesis.
mTOR Complex 1 (mTORC1) is compo ...
and
mTORC2 ''in vitro''. mTORC1 and mTORC2 can both inhibit DEPTOR through
phosphorylation.
Metabolism
DEPTOR cell-autonomously regulates
adipogenesis Adipogenesis is the formation of adipocytes (fat cells) from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as preadipocy ...
. In the muscle, Baf60c promotes a switch from oxidative to glycolytic myofiber type through DEPTOR-mediated
Akt/PKB activation. Within the brain, DEPTOR is highly expressed in the
hippocampus
The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...
, the medio-basal
hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
and the
circumventricular organs
Circumventricular organs (CVOs) ( circum-: around ; ventricular: of ventricle) are structures in the brain characterized by their extensive and highly permeable capillaries, unlike those in the rest of the brain where there exists a bloodâ ...
. Overexpression of DEPTOR in the medio-basal hypothalamus protects mice against high-fat diet-induced
obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
by modulating
Akt/PKB signaling.
Clinical cancer
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.
References
Further reading
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