TBC1D7 Is a Third Subunit of the TSC1-TSC2 Complex Upstream of mTORC1
Open accessAbstract
The tuberous sclerosis complex (TSC) tumor suppressors form the TSC1-TSC2 complex, which limits cell growth in response to poor growth conditions. Through its GTPase-activating protein (GAP) activity toward Rheb, this complex inhibits the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), a key promoter of cell growth. Here, we identify and biochemically characterize TBC1D7 as a stably associated and ubiquitous third core subunit of the TSC1-TSC2 complex. We demonstrate that the TSC1-TSC2-TBC1D7 (TSC-TBC) complex is the functional complex that senses specific cellular growth conditions and possesses Rheb-GAP activity. Sequencing analyses of samples from TSC patients suggest that TBC1D7 is unlikely to represent TSC3. TBC1D7 knockdown decreases the association of TSC1 and TSC2 leading to decreased Rheb-GAP activity, without effects on the localization of TSC2 to the lysosome. Like the other TSC-TBC components, TBC1D7 knockdown results in increased mTORC1 signaling, delayed induction of autophagy, and enhanced cell growth under poor growth conditions.
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TBC1D7 is a constitutive member of the TSC complex.
“A third subunit of TSCC, TBC1D7, was later discovered and shown to be a constitutive member of the complex (Dibble et al., 2012).”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Dibble et al., 2012
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- Authors
- Dibble, C. C., Elis, W., Menon, S., Qin, W., Klekota, J., Asara, J. M., Finan, P. M., Kwiatkowski, D. J., Murphy, L. O., & Manning, B. D.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Manning, Brendan D.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 47
- Issue
- 4
- Pages
- 535-546
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3693578
- OpenAlex
- W1985754630
- Cited by
- 612
- References
- 52
- Citations by year
- 2026: 16 · 2025: 34 · 2024: 39 · 2023: 49 · 2022: 45 · 2021: 57 · 2020: 49 · 2019: 39 · 2018: 60 · 2017: 47 · 2016: 46 · 2015: 51 · 2014: 45 · 2013: 31 · 2012: 4
- FWCI
- 16.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA122617, P01CA120964, P30CA006516)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- TSC1/TSC2 complex, tuberous sclerosis complex, mTORC1, autophagy, cell growth regulation, tumor suppressor signaling
- MeSH terms
- Ras Homolog Enriched in Brain Protein, Mechanistic Target of Rapamycin Complex 1, Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Amino Acid Sequence, Carrier Proteins, HeLa Cells, Humans, Lysosomes, Molecular Sequence Data, Neuropeptides, Protein Binding, Proteins, Tumor Cells, Cultured, Signal Transduction, Monomeric GTP-Binding Proteins, GTPase-Activating Proteins, Tumor Suppressor Proteins, Multiprotein Complexes, Intracellular Signaling Peptides and Proteins, HEK293 Cells, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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