The TSC1-TSC2 complex consists of multiple TSC1 and TSC2 subunits
Open accessAbstract
Background: Mutations to the TSC1 and TSC2 genes cause the disease tuberous sclerosis complex. The TSC1 and TSC2 gene products form a protein complex that integrates multiple metabolic signals to regulate the activity of the target of rapamycin (TOR) complex 1 (TORC1) and thereby control cell growth. Here we investigate the quaternary structure of the TSC1-TSC2 complex by gel filtration and coimmunoprecipitation. Results: TSC1 and TSC2 co-eluted in high molecular weight fractions by gel filtration. Coimmunoprecipitation of distinct tagged TSC1 and TSC2 isoforms demonstrated that TSC1-TSC2 complexes contain multiple TSC1 and TSC2 subunits. Conclusions: TSC1 and TSC2 interact to form large complexes containing multiple TSC1 and TSC2 subunits.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Chromatographic analyses suggest that TSCCs also contain multiple copies of TSC1 and TSC2, and it is postulated that including multiple copies of each constituent protein may increase the sensitivity of the complex to allosteric regulation.
“Chromatographic analyses suggest that TSCCs also contains multiple copies of TSC1 and TSC2, and it is postulated that including multiple copies of each constituent protein may increase the sensitivity of the complex to allosteric regulation (Hoogeveen-Westerveld et al., 2012).”
From Signal integration in the (m)TORC1 growth pathway (2018) · cites this paper as Hoogeveen-Westerveld et al., 2012
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Dan, H. C., Sun, M., Yang, L., Feldman, R. I., Sui, X.-M., Ou, C. C., Nellist, M. D., Yeung, R. S. W., Halley, D. J. J., Nicosia, S. V., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205838200 · Cited by 370 · see citing works
Self-citationRetractedDefining the role of mTOR in cancer
Guertin, D. A., & Sabatini, D. M. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.05.008 · Cited by 2,833 · see citing works
The Tuberous Sclerosis Complex
Crino, P. B., Nathanson, K. L., & Henske, E. P. (2006) · New England Journal of Medicine · doi:10.1056/nejmra055323 · Cited by 1,793 · see citing works
Identification of the Tuberous Sclerosis Gene <i>TSC1</i> on Chromosome 9q34
Slegtenhorst, M. V., Hoogt, R. D., Hermans, C., Nellist, M., Janssen, B., Verhoef, S., Lindhout, D., Ouweland, A. V. D., Halley, D., Young, J., et al. (1997) · Science · doi:10.1126/science.277.5327.805 · Cited by 1,648 · see citing works
Self-citationIdentification and characterization of the tuberous sclerosis gene on chromosome 16
(1993) · Cell · doi:10.1016/0092-8674(93)90618-z · Cited by 1,645 · see citing works
The TSC1–TSC2 complex: a molecular switchboard controlling cell growth
Huang, J., & Manning, B. D. (2008) · Biochemical Journal · doi:10.1042/bj20080281 · Cited by 1,237 · cited 1× · see citing works
“; licensee of the Creative Commons Attribution License distribution, and reproduction in any medium role of TSC1 is less clear [10].”
BackgroundDevys, D., Lutz, Y., Rouyer, N., Bellocq, J., & Mandel, J. (1993) · Nature Genetics · doi:10.1038/ng0893-335 · Cited by 781 · see citing works
Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products
van Slegtenhorst, M. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.6.1053 · Cited by 565 · see citing works
Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR
Zhang, H., Cicchetti, G., Onda, H., Koon, H. B., Asrican, K., Bajraszewski, N., Vázquez, F., Carpenter, C. L., & Kwiatkowski, D. J. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17222 · Cited by 538 · see citing works
Rheb fills a GAP between TSC and TOR
Manning, B. (2003) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2003.09.003 · Cited by 483 · see citing works
Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR
Zhang, H., Cicchetti, G., Onda, H., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317222 · Cited by 482 · see citing works
TSC2: filling the GAP in the mTOR signaling pathway
Li, Y. (2003) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2003.11.007 · Cited by 418 · see citing works
Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning
Cai, S.-L., Tee, A. R., Short, J. D., Bergeron, J. M., Kim, J., Shen, J., Guo, R., Johnson, C. L., Kiguchi, K., & Walker, C. L. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200507119 · Cited by 359 · see citing works
Benvenuto, G., Li, S., Brown, S. J., Braverman, R., Vass, W. C., Cheadle, J. P., Halley, D. J. J., Sampson, J. R., Wienecke, R., & DeClue, J. E. (2000) · Oncogene · doi:10.1038/sj.onc.1204009 · Cited by 253 · see citing works
Self-citationMolecular Organization of Target of Rapamycin Complex 2
Wullschleger, S., Loewith, R., Oppliger, W., & Hall, M. N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505553200 · Cited by 231 · see citing works
Localization of Rheb to the endomembrane is critical for its signaling function
Buerger, C., DeVries, B., & Stambolic, V. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.03.220 · Cited by 192 · see citing works
Characterization of the Cytosolic Tuberin-Hamartin Complex
Nellist, M. D., van Slegtenhorst, M. A., Goedbloed, M., van den Ouweland, A. M. W., Halley, D. J. J., & van der Sluijs, P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.50.35647 · Cited by 176 · see citing works
Self-citationAhmed, N. N., Franke, T. F., Bellacosa, A., Datta, K., Gonzalez-Portal, M. E., Taguchi, T., Testa, J. R., & Tsichlis, P. N. (1993) · PubMed · Cited by 160 · see citing works
Metastasis of benign tumor cells in tuberous sclerosis complex
Henske, E. P. (2003) · Genes Chromosomes and Cancer · doi:10.1002/gcc.10252 · Cited by 128 · see citing works
Wang, L., Rhodes, C. J., & Lawrence, J. C. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603566200 · Cited by 112 · see citing works
Regulation of TSC2 by 14-3-3 Binding
Li, Y., Inoki, K., Yeung, R. S. W., & Guan, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200510200 · Cited by 111 · see citing works
Caught in self-interaction: evolutionary and functional mechanisms of protein homooligomerization
Hashimoto, K., Nishi, H., Bryant, S. H., & Panchenko, A. R. (2011) · Physical Biology · doi:10.1088/1478-3975/8/3/035007 · Cited by 110 · see citing works
Nellist, M. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.25.2889 · Cited by 110 · see citing works
Self-citationA Ral GAP complex links PI 3-kinase/Akt signaling to RalA activation in insulin action
Chen, X.-W., Leto, D., Xiong, T., Yu, G., Cheng, A., Decker, S., & Saltiel, A. R. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e10-08-0665 · Cited by 108 · see citing works
Unusually mild tuberous sclerosis phenotype is associated withTSC2R905Q mutation
Jansen, A., Sancak, Ő., D’Agostino, D., Badhwar, A., Roberts, P. S., Gobbi, G., Wilkinson, R. D., Melanson, D., Tampieri, D. I., Koenekoop, R. K., et al. (2006) · Annals of Neurology · doi:10.1002/ana.21037 · Cited by 105 · see citing works
Self-citationHoogeveen‐Westerveld, M., Wentink, M. W. J., van den Heuvel, D., Mozaffari, M., Ekong, R., Povey, S., den Dunnen, J. T., Metcalfe, K., Vallee, S. E., Krueger, S., et al. (2011) · Human Mutation · doi:10.1002/humu.21451 · Cited by 91 · see citing works
Self-citationTamanini, F., van Unen, L., Bakker, C. E., Sacchi, N., GALJAARD, H., Oostra, B. A., & Hoogeveen, A. T. (1999) · Biochemical Journal · doi:10.1042/bj3430517 · Cited by 88 · see citing works
Self-citationShirakawa, R., Fukai, S., Kawato, M., Higashi, T., Kondo, H., Ikeda, T., Nakayama, E., Okawa, K., Nureki, O., Kimura, T., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.012112 · Cited by 86 · see citing works
Nellist, M. D., Sancak, Ő., Goedbloed, M., Rohé, C. F., van Netten, D., Mayer, K., Williams, A. T., van den Ouweland, A. M. W., & Halley, D. J. J. (2004) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201276 · Cited by 81 · see citing works
Self-citationIdentification and Characterization of the Interaction between Tuberin and 14-3-3ζ
Nellist, M. D., Goedbloed, M., de Winter, C., Verhaaf, B., Jankie, A., Reuser, A. J. J., van den Ouweland, A. M. W., van der Sluijs, P., & Halley, D. J. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204802200 · Cited by 75 · see citing works
Self-citationTakahara, T., Hara, K., Yonezawa, K., Sorimachi, H., & Maeda, T. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606087200 · Cited by 68 · see citing works
A reliable cell-based assay for testing unclassified TSC2 gene variants
Coevoets, R., Arican, S., Hoogeveen‐Westerveld, M., Simons, E. J., van den Ouweland, A. M. W., Halley, D. J. J., & Nellist, M. D. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.184 · Cited by 28 · see citing works
Self-citationAnalysis of TSC1 truncations defines regions involved in TSC1 stability, aggregation and interaction
Hoogeveen-Westerveld, M., Exalto, C., Maat-Kievit, A., van den Ouweland, A., Halley, D., & Nellist, M. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.06.004 · Cited by 25 · see citing works
Self-citationAdipocytes contain a novel complex similar to the tuberous sclerosis complex
Gridley, S., Chavez, J. A., Lane, W. S., & Lienhard, G. E. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2006.01.002 · Cited by 23 · see citing works
Wharton, C. W., & Eisenthal, R. (1981) · Springer eBooks · doi:10.1007/978-1-4615-8532-9 · Cited by 14 · see citing works
N-terminal hamartin-binding and C-terminal GAP domain of tuberin can separate in vivo
Momose, S., Kobayashi, T., Tada, N., Itoyama, S., & Hino, O. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.03.036 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Regulation of mTORC1 by PI3K Signaling
Dibble, C. C., & Cantley, L. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.06.002 · Cited by 770 · see citing works
Menon, S., Dibble, C. C., Talbott, G., Hoxhaj, G., Valvezan, A., Takahashi, H., Cantley, L., & Manning, B. (2014) · Cell · doi:10.1016/j.cell.2013.11.049 · Cited by 787 · see citing works
Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity
Carroll, B., Maetzel, D., Maddocks, O., Otten, G., Ratcliff, M., Smith, G. R., Dunlop, E., Passos, J., Davies, O. R., Jaenisch, R., et al. (2016) · eLife · doi:10.7554/elife.11058 · Cited by 177 · see citing works
Structural insights into TSC complex assembly and GAP activity on Rheb
Yang, H., Yu, Z., Chen, X., Li, J., Li, N., Cheng, J., Gao, N., Yuan, H., Ye, D., Guan, K., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20522-4 · Cited by 109 · see citing works
Yuan, F., Shi, M., Ji, J., Shi, H., Zhou, C., Yu, Y., Liu, B., Zhu, Z., & Zhang, J. (2014) · International Journal of Biological Sciences · doi:10.7150/ijbs.9773 · Cited by 63 · see citing works
TSC1 binding to lysosomal PIPs is required for TSC complex translocation and mTORC1 regulation
Fitzian, K., Brückner, A., Brohée, L., Zech, R., Antoni, C., Kiontke, S., Gasper, R., Matos, A. L. L., Beel, S., Wilhelm, S., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.04.019 · Cited by 60 · see citing works
Self-citationNellist, M. D., Schot, R., Hoogeveen‐Westerveld, M., Neuteboom, R. F., van der Louw, E. J. T. M., Lequin, M. H., Heus, K. B., Sibbles, B. J., de Coo, I. F. M., Brooks, A. S., et al. (2014) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2014.11.018 · Cited by 50 · see citing works
Self-citationUnderstanding human DNA variants affecting pre-mRNA splicing in the NGS era
Dufner‐Almeida, L. G., do Carmo, R. T., Masotti, C., & Haddad, L. A. (2019) · Advances in genetics · doi:10.1016/bs.adgen.2018.09.002 · Cited by 46 · see citing works
Modulation of TSC-mTOR signaling on immune cells in immunity and autoimmunity
Yang, H., Wang, X., Zhang, Y., Liu, H., Liao, J., Shao, K., Chu, Y., & Liu, G. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24426 · Cited by 44 · see citing works
Gai, Z., Chu, W., Deng, W., Li, W., Li, H. L., He, A., Nellist, M. D., & Wu, G. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw001 · Cited by 39 · see citing works
Self-citationQin, J., Wang, Z., Hoogeveen-Westerveld, M., Shen, G., Gong, W., Nellist, M., & Xu, W. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.701870 · Cited by 37 · see citing works
Self-citationDufner‐Almeida, L. G., Nanhoe, S., Zonta, A., Hosseinzadeh, M., Kom‐Gortat, R., Elfferich, P., Schaaf, G., Kenter, A. T., Kümmel, D., Migone, N., et al. (2019) · Human Mutation · doi:10.1002/humu.23963 · Cited by 31 · see citing works
Self-citationZech, R., Kiontke, S., Mueller, U., Oeckinghaus, A., & Kümmel, D. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.732446 · Cited by 29 · see citing works
Wong, H. T., McCartney, D. L., Lewis, J. C., Sampson, J. R., Howe, C. J., & de Vries, P. J. (2015) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2015-103154 · Cited by 19 · see citing works
Wang, Y.-Y., Chen, C., Deng, Z.-Y., Bian, E.-B., Huang, C., Lei, T., Lv, X.-W., Liu, L.-P., & Li, J. (2017) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2016.12.062 · Cited by 11 · see citing works
Signal integration in the (m)TORC1 growth pathway
Ramlaul, K., & Aylett, C. H. S. (2018) · Frontiers in Biology · doi:10.1007/s11515-018-1501-7 · Cited by 12 · see citing works
Fu, W., & Wu, G. (2023) · Protein Science · doi:10.1002/pro.4731 · Cited by 7 · see citing works
UNBS5162 inhibits colon cancer growth via suppression of PI3K/Akt signaling pathway
Zhang, F., Hui-zeng, L., Liu, J.-M., Ye, X.-Y., & Wang, C. (2018) · médecine/sciences · doi:10.1051/medsci/201834f117 · Cited by 5 · see citing works
Dai, D. L., Hasan, S. M. N., Woollard, G., Abbas, Y. M., Bueler, S. A., Julien, J., Rubinstein, J. L., & Mazhab‐Jafari, M. T. (2021) · Biochemistry · doi:10.1021/acs.biochem.1c00269 · Cited by 3 · see citing works
Mutational and functional study of Tuberous Sclerosis Complex 1 and 2 genes (TSC1 and TSC2)
de Almeida, L. G. D. (2019) · doi:10.11606/t.41.2019.tde-27082019-100610 · Cited by 2 · see citing works
Nellist, M. D., Douben, H., Hoogeveen‐Westerveld, M., Louwen, J., Kroos, M. A., Punt, M., van Ommeren, B., van Unen, L., Elfferich, P., Kasteleijn, E., et al. (2022) · doi:10.22541/au.165217208.81458305/v1 · Cited by 1 · see citing works
Self-citationМалышева, И. Е., Балан, О. В., & Tikhonovich, E. L. (2025) · Tuberculosis and lung diseases · doi:10.58838/2075-1230-2025-103-5-52-56
- Authors
- Hoogeveen-Westerveld, M., van Unen, L., van den Ouweland, A., Halley, D., Hoogeveen, A., & Nellist, M.
- Affiliations
- Erasmus MC (NL)
- Corresponding author
- Nellist, Mark
- Venue
- BMC Biochemistry
- Published
- 2012-09-24
- Volume
- 13
- Issue
- 1
- Pages
- 18-18
- ISSN
- 1471-2091 (ISSN-L)
- PMC
- PMC3517901
- OpenAlex
- W2132804463
- Cited by
- 24
- References
- 35
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2019: 3 · 2018: 4 · 2016: 5 · 2015: 2 · 2014: 3 · 2013: 1
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- BMC Biochemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Keywords
- TSC1/TSC2 complex, tuberous sclerosis complex, cell growth regulation, protein-protein interaction, molecular weight
- MeSH terms
- Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Epitopes, Chromatography, Gel, Humans, Protein Isoforms, Protein Structure, Quaternary, Tumor Suppressor Proteins, Immunoprecipitation, 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 ›
Are you an author, or do you see a problem with this page? Request a review