DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival

Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, Gray NS, Sabatini DM · 2009 · Cell · Atlas ID PET2009

What this study shows

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.

Abstract

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The mTORC1 and mTORC2 pathways regulate cell growth, proliferation, and survival. We identify DEPTOR as an mTOR-interacting protein whose expression is negatively regulated by mTORC1 and mTORC2. Loss of DEPTOR activates S6K1, Akt, and SGK1, promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities. DEPTOR overexpression suppresses S6K1 but, by relieving feedback inhibition from mTORC1 to PI3K signaling, activates Akt. Consistent with many human cancers having activated mTORC1 and mTORC2 pathways, DEPTOR expression is low in most cancers.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cancer cell lines) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Human cancer cell lines
Journal	Cell
Year	2009
Peer reviewed	Yes
Record last updated	2026-08-22
Source	DOI 10.1016/j.cell.2009.03.046 · PMID 19446321 · Free full text (PMC2758791)

Extracted findings

Intervention	Genetic/biochemical (DEPTOR)
Target	DEPTOR / mTORC1 & mTORC2
Model	Human cancer cell lines
Effect	DEPTOR is an mTOR inhibitor overexpressed in multiple myeloma and required for myeloma-cell survival

In the Atlas

Cite this paper

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Peterson, T. R., Laplante, M., Thoreen, C. C., Sancak, Y., Kang, S. A., Kuehl, W. M., Gray, N. S., & Sabatini, D. M. (2009). DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. https://doi.org/10.1016/j.cell.2009.03.046

@article{PET2009,
  author       = {Peterson, T. R. and Laplante, M. and Thoreen, C. C. and Sancak, Y. and Kang, S. A. and Kuehl, W. M. and Gray, N. S. and Sabatini, D. M.},
  title        = {{DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival}},
  journal      = {Cell},
  year         = {2009},
  doi          = {10.1016/j.cell.2009.03.046},
  note         = {PMID: 19446321},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record PET2009) [Data set]. https://mtor-atlas.org/study/PET2009/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_PET2009,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record PET2009},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/PET2009/},
  doi          = {10.5281/zenodo.22059963}
}