Tuberous Sclerosis Complex Gene Products, Tuberin and Hamartin, Control mTOR Signaling by Acting as a GTPase-Activating Protein Complex toward Rheb

Abstract Mast cells play critical roles in allergic disorders and asthma. The importance of tuberous sclerosis complex 1/2-mammalian target of rapamycin (TSC1/2-mTOR) signaling in mast cells is unknown. Here, we report that TSC1 is a critical regulator for mTOR signaling in mast cells downstream of FcεRI and c-Kit, and differentially controls mast cell degranulation and cytokine production. TSC1-deficiency results in impaired mast cell degranulation, but enhanced cytokine production in vitro and in vivo after FcεRI engagement. Furthermore, TSC1 is critical for mast cell survival through multiple pathways of apoptosis including the down-regulation of p53, miR-34a, reactive oxygen species, and the up-regulation of Bcl-2. Together, these findings reveal that TSC1 is a critical regulator of mast cell activation and survival, suggesting the manipulation of the TSC1/2-mTOR pathway as a therapeutic strategy for mast cell-mediated diseases.

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Fetal Brain mTOR Signaling Activation in Tuberous Sclerosis Complex

Cerebral Cortex ◽

10.1093/cercor/bhs310 ◽

2012 ◽

Vol 24 (2) ◽

pp. 315-327 ◽

Cited By ~ 53

Author(s):

Victoria Tsai ◽

Whitney E. Parker ◽

Ksenia A. Orlova ◽

Marianna Baybis ◽

Anthony W.S. Chi ◽

...

Keyword(s):

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Fetal Brain ◽

Mtor Signaling ◽

Signaling Activation

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mTOR Signaling and Neural Stem Cells: The Tuberous Sclerosis Complex Model

International Journal of Molecular Sciences ◽

10.3390/ijms19051474 ◽

2018 ◽

Vol 19 (5) ◽

pp. 1474 ◽

Cited By ~ 6

Author(s):

Alice Polchi ◽

Alessandro Magini ◽

Danila Meo ◽

Brunella Tancini ◽

Carla Emiliani

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Complex Model ◽

Mtor Signaling

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Everolimus treatment in a 3-month-old infant with tuberous sclerosis complex cardiac rhabdomyoma, severe left ventricular outflow tract obstruction, and hearing loss

Cardiology in the Young ◽

10.1017/s1047951121000639 ◽

2021 ◽

pp. 1-4

Author(s):

Mecnun Çetin ◽

Aysun A. Aydın ◽

Kamuran Karaman

Keyword(s):

Hearing Loss ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Protein Complex ◽

Left Ventricular Outflow Tract ◽

Ventricular Outflow Tract ◽

Left Ventricular ◽

Outflow Tract ◽

The Body ◽

Left Ventricular Outflow

Abstract Tuberous sclerosis complex is a rare multisystem genetic disorder characterised by the growth of numerous tumour-like malformations in many parts of the body including skin, kidneys, brain, lung, eyes, liver, and heart. Mutations in the TSC1 or TSC2 genes have been reported to cause disruption in the TSC1–TSC2 intracellular protein complex, causing over-activation of the mammalian target of rapamycin protein complex. In this study, we present a 3-month-old male infant diagnosed with tuberous sclerosis, bilateral neurosensorial hearing loss, Wolff–Parkinson–White syndrome on electrocardiography, multiple cardiac rhabdomyomas with severe stenosis in the left ventricular outflow tract, who responded well to the Everolimus therapy.

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