DEPTOR
Endogenous inhibitor of both mTORC1 and mTORC2; paradoxically overexpressed in a subset of multiple myelomas, which depend on high DEPTOR: partial mTORC1 suppression relieves S6K1-IRS1 feedback and sustains PI3K/Akt survival signalling (Peterson 2009).
An in-built damper on both complexes. A natural brake on both mTOR complexes at once. Oddly, some multiple myeloma (bone marrow cancer) cells make extra amounts of it and depend on having it: damping mTORC1 releases a feedback loop and keeps PI3K/Akt survival signaling switched on.
Overexpressed in a subset of multiple myeloma, and those cells need it: knockdown kills them (PET2009). An inhibitor of the pathway that the tumour is nonetheless addicted to.
TL;DR. DEPTOR appears in 2 curated studies in Oliver's mTOR Atlas: 2 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 1 interaction in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| DEPTOR inhibits mTOR mechanism: binding · this link in full · on the map table | DEPTOR sits on mTOR and dampens both complexes; some cancer cells (myeloma) make extra DEPTOR and come to depend on that damping. DEPTOR sits on mTOR and damps both complexes; myeloma cells overexpress it and depend on that damping. DEPTOR sits on mTOR and damps both complexes; myeloma cells overexpress it and depend on that damping. Holds under: One study in human cancer cell lines (PET2009), centred on myeloma. Not replicated in this corpus and not shown in other cell types, in animals or in patients. plausible in people, not shown directly · settled in the literature | M | PET2009 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| M | Molecular — cells, biochemistry, structure | 2 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2026 | M | Phosphorylation of OTUB1 promotes autophagy initiation under starvation SUN2026B Under starvation, ERK phosphorylates the deubiquitinase OTUB1 at S118, which stabilizes it by letting it out-compete TRIM29 for binding to ANXA2. Stabilized OTUB1 upregulates DEPTOR, a natural mTOR inhibitor, which suppresses mTOR and triggers autophagy. In mice, restoring this fasting-triggered ERK-OTUB1-DEPTOR-mTOR axis countered the mTOR-activating effect of a Western diet and eased MASLD (fatty liver disease) progression, giving a mechanistic account of how fasting benefits the liver. |
| 2009 | M | DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival PET2009 Identified DEPTOR as a built-in brake on BOTH mTOR complexes. The twist: in some multiple myelomas DEPTOR is overexpressed, which by relieving a feedback loop actually keeps pro-survival Akt signaling ON - a neat example of how an 'inhibitor' can be co-opted by cancer. |
Related entities
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