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TSC1/TSC2 signaling in the CNS
Open accessAbstract
Over the past several years, the study of a hereditary tumor syndrome, tuberous sclerosis complex (TSC), has shed light on the regulation of cellular proliferation and growth. TSC is an autosomal dominant disorder that is due to inactivating mutations in TSC1 or TSC2 and characterized by benign tumors (hamartomas) involving multiple organ systems. The TSC1/2 complex has been found to play a crucial role in an evolutionarily-conserved signaling pathway that regulates cell growth: the mTORC1 pathway. This pathway promotes anabolic processes and inhibits catabolic processes in response to extracellular and intracellular factors. Findings in cancer biology have reinforced the critical role for TSC1/2 in cell growth and proliferation. In contrast to cancer cells, in the CNS, the TSC1/2 complex not only regulates cell growth/proliferation, but also orchestrates an intricate and finely tuned system that has distinctive roles under different conditions, depending on cell type, stage of development, and subcellular localization. Overall, TSC1/2 signaling in the CNS, via its multi-faceted roles, contributes to proper neural connectivity. Here, we will review the TSC signaling in the CNS.
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“This then binds and activates phosphoinositide-dependent protein kinase (PDK1), which in turn contributes to activation of the serine/threonine protein kinase Akt proteins.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [67]
In the citing paper
“Activated Akt phosphorylates TSC2, reducing its GTPase activating protein (GAP) activity for the Ras family GTPase, Rheb.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [67]
In the citing paper
“BDNF binding to TrkB activates the phosphatidylinositol-3-OH kinase (PI(3)K), which phosphorylates phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) at the 3′ position to generate phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3).”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [67]
In the citing paper
“Thus, phosphorylation of TSC2 leads to Rheb activation, which in turn triggers activation of the protein kinase mTOR, contributing to the activation of protein synthesis (Fig. 4)67.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [67]
In the citing paper
“This disorder is caused by mutations in TSC1 or TSC2 that encode tumour suppressor proteins which form the complex TSC1–TSC2 that regulate protein synthesis in a wide range of mammalian cell types, including neurons67.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [67]
In the citing paper
“The binding of growth factors to receptor tyrosine kinases leads to phosphorylation of the TSC complex and subsequent activation of the mTOR, a positive regulator of protein synthesis67.”
From Activity-dependent neuronal signalling and autism spectrum disorder (2013) · cites this paper as [67]
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Groß, C., & Bhattacharya, A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804461-2.00011-1 · Cited by 3
Viewing Animal Models for Tuberous Sclerosis Complex in the Light of Evolution
Howe, C. J., Serfontein, J., Nisbet, R. E. R., & de Vries, P. J. (2014) · Neuromethods · doi:10.1007/978-1-4939-2250-5_4 · Cited by 3
Complejo de esclerosis tuberosa
Ubarnes, M. B., González, R. F., & Kleebauer, C. G. (2020) · Revista Ciencias Biomédicas · doi:10.32997/rcb-2015-2967 · Cited by 2
Huson, S., & Korf, B. R. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-383834-6.00128-2 · Cited by 1
Progress Toward Therapies and Interventions for Neurodevelopmental Disorders
Ajetunmobi, A., & Tropea, D. (2015) · Wiley eBooks · doi:10.1002/9781118524947.ch14 · Cited by 1
FOCUS ON… Ubiquitin‐related tumor suppressors
Just, W. W. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.04.006 · Cited by 1
Changes in Language Pathways in Tuberous Sclerosis Complex Patients with Autism
Angeles, W. W. L.-D. L. (2014) · Digital Access to Scholarship at Harvard (DASH) (Harvard University) · Cited by 1
Focus on … LKB1/AMPK signaling
Just, W. W. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.03.011
IMPLICATIONS OF MITOTIC ONSET REGULATION IN TUBEROUS SCLEROSIS
Dare-Shih, J. (2016) · Scholarship at UWindsor (University of Windsor)
New approaches to understand dynamics of protein synthesis in neurons
Chow, A., & Ikeuchi, Y. (2017) · 生産研究 · doi:10.11188/seisankenkyu.69.115
Gipson, T. (2018) · Springer eBooks · doi:10.1007/978-3-319-98414-8_19
Сигнальные каскады белкового фосфорилирования при аутизме (с акцентом на путь mTOR)
Бокша, И. С., Prokhorova, T. A., Терешкина, Е. Б., Savushkina, O. K., & Бурбаева, Г. Ш. (2021) · Biochemistry (Moscow) · doi:10.31857/s0320972521050031
Aksoylu, I. S., Martin, P., Robert, F., Szkop, K. J., Redmond, N. E., Chen, S., Beauchamp, R. L., Nobeli, I., Pelletier, J., Larsson, O. S., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-2702044/v1
Molecular Pathology of Kidney Tumors
Al‐Obaidy, K. I., Alruwaii, Z. I., Mohanty, S. K., Liang Cheng, C., & Williamson, S. R. (2023) · Springer eBooks · doi:10.1007/978-3-031-35118-1_13
Metadata
- Authors
- Han, J. M., & Sahin, M.
- Affiliations
- Boston Children's Hospital (US)
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2011-02-15
- Volume
- 585
- Issue
- 7
- Pages
- 973-980
- ISSN
- 0014-5793 (ISSN-L)
- PMC
- PMC3070766
- OpenAlex
- W2074197666
- Cited by
- 105
- References
- 123
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 10 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 2 · 2017: 10 · 2016: 4 · 2015: 9 · 2014: 13 · 2013: 14 · 2012: 10
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01NS058956)
- 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 › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- tuberous sclerosis complex, TSC1, TSC2, mTORC1 signaling, central nervous system, neural cell proliferation, neural growth, neuronal connectivity, hamartoma, cell growth regulation
- MeSH terms
- Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Animals, Central Nervous System, Disease Models, Animal, Humans, Neurons, Tuberous Sclerosis, Signal Transduction, Tumor Suppressor Proteins
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