Cited by 235Tuberous Sclerosis Complex ResearchPI3K/AKT/mTOR signaling in cancerTGF-β signaling in diseases

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TSC1 Stabilizes TSC2 by Inhibiting the Interaction between TSC2 and the HERC1 Ubiquitin Ligase

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Chong-Kopera, Huira, Inoki, Ken, Li, Yong, Zhu, Tianqing, Garcia-Gonzalo, Francesc R., Rosa, Jose Luis, Guan, Kun-Liang·2006·Journal of Biological Chemistry

DOI 10.1074/jbc.c500451200

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Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by hamartoma formation in various organs. Two genes responsible for the disease, TSC1 and TSC2, have been identified. The TSC1 and TSC2 proteins, also called hamartin and tuberin, respectively, have been shown to regulate cell growth through inhibition of the mammalian target of rapamycin pathway. TSC1 is known to stabilize TSC2 by forming a complex with TSC2, which is a GTPase-activating protein for the Rheb small GTPase. We have identified HERC1 as a TSC2-interacting protein. HERC1 is a 532-kDa protein with an E3 ubiquitin ligase homology to E6AP carboxyl terminus (HECT) domain. We observed that the interaction of TSC1 with TSC2 appears to exclude TSC2 from interacting with HERC1. Disease mutations in TSC2, which result in its destabilization, allow binding to HERC1 in the presence of TSC1. Our study reveals a potential molecular mechanism of how TSC1 stabilizes TSC2 by excluding the HERC1 ubiquitin ligase from the TSC2 complex. Furthermore, these data reveal a possible biochemical basis of how certain disease mutations inactivate TSC2.

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Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083
Self-citation
Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression
Fingar, D. C., & Blenis, J. (2004) · Oncogene · doi:10.1038/sj.onc.1207542 · Cited by 1,264
Akt regulates growth by directly phosphorylating Tsc2
Potter, C. J., Pedraza, L. G., & Xu, T. (2002) · Nature Cell Biology · doi:10.1038/ncb840 · Cited by 959
Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins
Zhang, Y., Gao, X., Saucedo, L. J., Ru, B., Edgar, B. A., & Pan, D. (2003) · Nature Cell Biology · doi:10.1038/ncb999 · Cited by 924
Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling
Tee, A. R., Fingar, D. C., Manning, B. D., Kwiatkowski, D. J., Cantley, L. C., & Blenis, J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.202476899 · Cited by 827
Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1
Bischoff, F. R., & Ponstingl, H. (1991) · Nature · doi:10.1038/354080a0 · Cited by 711
Tsc tumour suppressor proteins antagonize amino-acid–TOR signalling
Gao, X., Zhang, Y., Arrazola, P., Hino, O., Kobayashi, T., Yeung, R. S. W., Ru, B., & Pan, D. (2002) · Nature Cell Biology · doi:10.1038/ncb847 · Cited by 689
A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells
Kwiatkowski, D. J. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.5.525 · Cited by 674
The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases
Jackson, P. K., Eldridge, A. G., Freed, E., Furstenthal, L., Hsu, J. Y., Kaiser, B. K., & Reimann, J. D. R. (2000) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)01834-1 · Cited by 635

Show all 30 references

Research works printed but not linked: 1

Zhang, 2003, J. Clin. Invest., 112, 1223, 10.1172/JCI200317222 · DOI

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Everolimus improves neuropsychiatric symptoms in a patient with tuberous sclerosis carrying a novel TSC2 mutation
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Cancer-associated dynamics and potential regulators of intronic polyadenylation revealed by IPAFinder using standard RNA-seq dataPreprint
Zhao, Z., Xu, Q., Wei, R., Wang, W., Ding, D., Yang, Y., Yao, J., Zhang, L., Hu, Y., Wei, G., et al. (2021) · Genome Research · doi:10.1101/gr.271627.120 · Cited by 40
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Qin, 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
An Autoinhibited Noncanonical Mechanism of GTP Hydrolysis by Rheb Maintains mTORC1 Homeostasis
Mazhab-Jafari, M. T., Marshall, C. B., Ishiyama, N., Ho, J., Di Palma, V., Stambolic, V., & Ikura, M. (2012) · Structure · doi:10.1016/j.str.2012.06.013 · Cited by 37
The E3 ubiquitin ligase HERC1 controls the ERK signaling pathway targeting C-RAF for degradation
Schneider, T., Martinez-Martinez, A., Cubillos‐Rojas, M., Bartrons, R., Ventura, F., & Rosa, J. L. (2018) · Oncotarget · doi:10.18632/oncotarget.25847 · Cited by 37
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Aberrant expression of TSC2 gene in the newly diagnosed acute leukemia
Xu, Z., Wang, M., Wang, L., Wang, Y., Zhao, X., Rao, Q., & Wang, J. (2009) · Leukemia Research · doi:10.1016/j.leukres.2009.01.041 · Cited by 38
Identification of TBC7 having TBC domain as a novel binding protein to TSC1–TSC2 complex
Nakashima, A., Yoshino, K., Miyamoto, T., Eguchi, S., Oshiro, N., Kikkawa, U., & Yonezawa, K. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.07.011 · Cited by 36
RUNX1/EGFR pathway contributes to STAT3 activation and tumor growth caused by hyperactivated mTORC1
Lin, W., Wan, X., Sun, A., Zhou, M., Chen, X., Li, Y., Wang, Z., Huang, H., Li, H., Chen, X., et al. (2021) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2021.10.009 · Cited by 36
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Nguyen, T. P., Frank, A. R., & Jewell, J. L. (2017) · Cellular Logistics · doi:10.1080/21592799.2017.1378794 · Cited by 37
Highly homologous HERC proteins localize to endosomes and exhibit specific interactions with hPLIC and Nm23B
Hochrainer, K., Kroismayr, R., Baranyi, U., Binder, B. R., & Lipp, J. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8148-5 · Cited by 34
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Shen, Y., Goncharov, D. A., Pena, A. Z., Baust, J., Barragan, A. C., Ray, A., Rode, A., Bachman, T. N., Chang, B., Jiang, L., et al. (2022) · Science Signaling · doi:10.1126/scisignal.abn2743 · Cited by 34
The E3 ubiquitin ligase Peli1 regulates the metabolic actions of mTORC1 to suppress antitumor T cell responses
Ko, C., Zhang, L., Jie, Z., Zhu, L., Zhou, X., Xie, X., Gao, T., Yang, J., Cheng, X., & Sun, S. (2020) · The EMBO Journal · doi:10.15252/embj.2020104532 · Cited by 34
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Ramlaul, K., Fu, W., Li, H., de Martin Garrido, N., He, L., Trivedi, M., Cui, W., Aylett, C. H. S., & Wu, G. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.166743 · Cited by 34
Rheb regulates nuclear mTORC1 activity independent of farnesylation
Zhong, Y., Zhou, X., Guan, K., & Zhang, J. (2022) · Cell chemical biology · doi:10.1016/j.chembiol.2022.02.006 · Cited by 34
Self-citation
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Fortier, A.-M., Asselin, É., & Cadrin, M. (2011) · BioMolecular Concepts · doi:10.1515/bmc.2011.003 · Cited by 28
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Pérez-Villegas, E. M., Ruiz, R., Bachiller, S., Ventura, F., Armengol, J. A., & Rosa, J. L. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.11.017 · Cited by 32
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Crystal structure of the yeast TSC1 core domain and implications for tuberous sclerosis pathological mutations
Sun, W., Zhu, Y. J., Wang, Z., Zhong, Q., Gao, F., Lou, J., Gong, W., & Xu, W. (2013) · Nature Communications · doi:10.1038/ncomms3135 · Cited by 27
Sustained activation of mTORC1 in macrophages increases AMPKα-dependent autophagy to maintain cellular homeostasis
Pan, H., Zhong, X., & Lee, S. (2016) · BMC Biochemistry · doi:10.1186/s12858-016-0069-6 · Cited by 27
VPS34 regulates TSC1/TSC2 heterodimer to mediate RheB and mTORC1/S6K1 activation and cellular transformation
Mohan, N., Shen, Y., Dokmanovic, M., Endo, Y., Hirsch, D. S., & Wu, W. J. (2016) · Oncotarget · doi:10.18632/oncotarget.10469 · Cited by 28
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TSC1/TSC2 inactivation inhibits AKT through mTORC1‐dependent up‐regulation of STAT3‐PTEN cascade
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Gürsoy, S., & Erçal, D. (2018) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2018.08.006 · Cited by 24
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Qin, X., Wang, X., Liu, F., Morris, L. E., Wang, X., Jiang, B., & Zhang, Y. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.03.013 · Cited by 23
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Tchevkina, E. M., & Komelkov, A. V. (2012) · InTech eBooks · doi:10.5772/48274 · Cited by 26
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Zhu, J., & Tsai, N. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2019.12.030 · Cited by 24
Tsc1 regulates tight junction independent of mTORC1
Lai, M., Zou, W., Han, Z., Zhou, L., Qiu, Z., Chen, J., Zhang, S., Lai, P., Li, K., Zhang, Y., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2020891118 · Cited by 22
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Zheltukhin, A. O., & Chumakov, P. M. (2010) · Biochemistry (Moscow) · doi:10.1134/s0006297910130110 · Cited by 23
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España, J., Tuveson, D. A., Adams, D. J., & Matakidou, A. (2015) · Scientific Reports · doi:10.1038/srep11061 · Cited by 21
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Kladney, R. D., Cardiff, R. D., Kwiatkowski, D. J., Chiang, G. G., Weber, J. D., Arbeit, J. M., & Lu, Z. H. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1646 · Cited by 21
Role of Tumor Suppressor TSC1 in Regulating Antigen-Specific Primary and Memory CD8 T Cell Responses to Bacterial Infection
Krishna, S., Yang, J., Wang, H., Qiu, Y., & Zhong, X. (2014) · Infection and Immunity · doi:10.1128/iai.01816-14 · Cited by 20
The HERC1 ubiquitin ligase regulates presynaptic membrane dynamics of central synapses
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Self-citation
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Lin, C., Traets, J. J. H., Vredevoogd, D. W., Visser, N. L., & Peeper, D. S. (2023) · The EMBO Journal · doi:10.15252/embj.2022111614 · Cited by 19
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Self-citation
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Segreto, R., Bazafkan, H., Millinger, J., Schenk, M., Atanasova, L., Doppler, M., Bueschl, C., Boeckstaens, M., Diaz, S. S., Schreiner, U., et al. (2021) · PLoS ONE · doi:10.1371/journal.pone.0262180 · Cited by 17
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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
microRNA 92b-3p regulates primordial follicle assembly by targeting TSC1 in neonatal mouse ovaries
Li, T., Liu, X., Gong, X., Qiukai, E., Zhang, X., & Zhang, X. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1593648 · Cited by 18
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Hari, A. S., Banerji, R., Liang, L., Fulton, R. E., Huynh, C. Q., Fabisiak, T., McElroy, P. B., Roede, J. R., & Patel, M. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102895 · Cited by 17
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Ma, M., Dai, J., Xu, T., Yu, S., Yu, H., Tang, H., Yan, J., Wu, X., Yu, J., Chi, Z., et al. (2017) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-017-2550-z · Cited by 17
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Seibert, M., Kurrle, N., Schnütgen, F., & Serve, H. L. (2021) · Matrix Biology · doi:10.1016/j.matbio.2021.01.001 · Cited by 18
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Huang, Z., & Wells, D. (2011) · Cambridge University Press eBooks · doi:10.1017/cbo9780511921896.013 · Cited by 15
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Ohsawa, M., Kobayashi, T., Okura, H., Igarashi, T., Mizuguchi, M., & Hino, O. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054503 · Cited by 15
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Pignatelli, M., Feligioni, M., Piccinin, S., Molinaro, G., Nicoletti, F., & Nisticò, R. (2013) · Current Pharmaceutical Design · doi:10.2174/1381612811319360008 · Cited by 14
Response of Lymphangioleiomyomatosis to a Mammalian Target of Rapamycin Inhibitor (Temsirolimus) –Based Treatment
Piha-Paul, S. A., Hong, D. S., & Kurzrock, R. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.32.5928 · Cited by 14
Atypical tuberous sclerosis complex presenting as familial renal cell carcinoma with leiomyomatous stroma
Bah, I., Fahiminiya, S., Bégin, L. R., Hamel, N., D’Agostino, D., Tanguay, S., & Foulkes, W. D. (2018) · The Journal of Pathology Clinical Research · doi:10.1002/cjp2.104 · Cited by 13
The evolution and diversification of the Hsp90 co-chaperone system
Engler, S., & Büchner, J. (2025) · Biological Chemistry · doi:10.1515/hsz-2025-0112 · Cited by 12
Hamartin Variants That Are Frequent in Focal Dysplasias and Cortical Tubers Have Reduced Tuberin Binding and Aberrant Subcellular Distribution In Vitro
Lugnier, C., Majores, M., Fassunke, J., Pernhorst, K., Niehusmann, P., Simon, M., Nellist, M. D., Schoch, S., & Becker, A. J. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181b9a699 · Cited by 12
The Role of Heat Shock Protein-90 in the Pathogenesis of Birt-Hogg-Dubé and Tuberous Sclerosis Complex Syndromes
Woodford, M. R., Backe, S. J., Sager, R., Bourboulia, D., Bratslavsky, G., & Mollapour, M. (2020) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2020.03.016 · Cited by 13
Tuberous sclerosis complex
Winden, K. D., Bebin, E. M., Jeste, S., Krueger, D. A., Paul, E., & Sahin, M. (2026) · Nature Reviews Disease Primers · doi:10.1038/s41572-026-00688-9 · Cited by 12
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Heritz, J. A., Backe, S. J., & Mollapour, M. (2024) · Oncotarget · doi:10.18632/oncotarget.28653 · Cited by 11
Biological function derived from predicted structures in CASP11
Huwe, P. J., Xu, Q., Shapovalov, M. V., Modi, V., Andrake, M., & Dunbrack, R. L. (2016) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24997 · Cited by 10
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Mrozek, E. M., Bajaj, V., Guo, Y., Malinowska, I. A., Zhang, J., & Kwiatkowski, D. J. (2021) · PLoS ONE · doi:10.1371/journal.pone.0248380 · Cited by 10
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Self-citation
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Li, S., Ren, C., Stone, C., Chandra, A., Xu, J., Li, N., Han, C., Ding, Y., Ji, X., & Shao, G. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.582368 · Cited by 9
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Ferreri, A., Lang, V., Kaufmann, R., & Buerger, C. (2022) · Cells · doi:10.3390/cells11182847 · Cited by 9
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Crino, P. B., & Tsai (2012) · Advances in Genomics and Genetics · doi:10.2147/agg.s19837 · Cited by 9
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Backe, S. J., Woodford, M. R., Ahanin, E. F., Sager, R., Bourboulia, D., & Mollapour, M. (2022) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-14740-1_11 · Cited by 8
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Inoue, H., Uyama, T., Suzuki, T., Kazami, M., Hino, O., Kobayashi, T., Kobayashi, K., Tadokoro, T., & Yamamoto, Y. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.12.054 · Cited by 8
Research Translation and Personalized Medicine
Brugarolas, J. (2012) · Springer eBooks · doi:10.1007/978-1-4614-2400-0_8 · Cited by 7
The TSC1–TSC2 Complex
(2010) · The Enzymes · doi:10.1016/s1874-6047(10)28002-2 · Cited by 8
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Sakamoto, H., Yamasaki, T., Sumiyoshi, T., Utsunomiya, N., Takeda, M., Kamba, T., Nakamura, E., & Ogawa, O. (2018) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2018-205211 · Cited by 6
Translational Medicine Strategies in Drug Development for Neurodevelopmental Disorders
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Authors: Chong-Kopera, H., Inoki, K., Li, Y., Zhu, T., Garcia-Gonzalo, F. R., Rosa, J. L., & Guan, K.-L.
Affiliations: University of Michigan (US)
Corresponding author: Guan, Kun-Liang
ORCID: Inoki, Ken
Li, Yong
Zhu, Tianqing
Guan, Kun-Liang
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2006-03
Volume: 281
Issue: 13
Pages: 8313-8316
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.c500451200
OpenAlex: W1984412362
Cited by: 234
References: 30
Citations by year: 2026: 9 · 2025: 9 · 2024: 4 · 2023: 6 · 2022: 10 · 2021: 13 · 2020: 11 · 2019: 6 · 2018: 11 · 2017: 14 · 2016: 18 · 2015: 7 · 2014: 11 · 2013: 12 · 2012: 21
FWCI: 10.19
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 5329 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, public-domain)
Funders: National Institute on Aging (T32-AG00114-18, T32AG000114)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK124709)
Topics: Health Sciences › Medicine › Genetics (clinical) › 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 › Molecular Biology › TGF-β signaling in diseases
Keywords: tuberous sclerosis complex, TSC1, TSC2, hamartin, tuberin, HERC1, E3 ubiquitin ligase, protein-protein interaction, protein stabilization, HECT domain, pathogenic variants, mTOR signaling, hamartoma
MeSH terms: Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Amino Acid Sequence, Animals, Brain Chemistry, Cell Extracts, Cell Line, Cycloheximide, Humans, Ligases, Precipitin Tests, Protein Synthesis Inhibitors, Blotting, Western, Silver Staining, Gene Deletion, Protein Structure, Tertiary, Guanine Nucleotide Exchange Factors, Protein Subunits, Tumor Suppressor Proteins, Ubiquitin, Ubiquitin-Protein Ligases, Mice

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TSC1 Stabilizes TSC2 by Inhibiting the Interaction between TSC2 and the HERC1 Ubiquitin Ligase

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