Abstract
The TSC1-TSC2 tumor suppressor complex serves as an interface between insulin and nutrient signaling pathways and the cell growth machinery. Recent work has indicated that the TSC1-TSC2 complex plays a role in the pathobiology of a number of tumor predisposition syndromes, including tuberous sclerosis (TSC1/2), Peutz-Jeghers syndrome (LKB1), and Cowden's syndrome (PTEN), in which the TSC/Rheb/mTOR axis is inappropriately active secondary to loss of tumor suppressor function. Recent work has demonstrated that TSC deficiency imposes a negative autoregulatory loop that suppresses insulin signaling at the post-receptor level, effectively resulting in cell autonomous insulin resistance. Exploitation of this insulin signaling deficiency may hold promise among tailored clinical therapies designed to manage tuberous sclerosis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Apoptosis / genetics
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Apoptosis / physiology
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Gene Expression Regulation
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Genetic Predisposition to Disease*
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Hamartoma Syndrome, Multiple / genetics
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Hamartoma Syndrome, Multiple / physiopathology
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Humans
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Insulin Receptor Substrate Proteins
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Insulin Resistance / genetics*
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Insulin Resistance / physiology
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Peutz-Jeghers Syndrome / genetics
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Peutz-Jeghers Syndrome / physiopathology
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Phosphoproteins / genetics
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Phosphoproteins / physiology
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Protein Processing, Post-Translational
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / physiology*
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Receptors, Thyroid Hormone / genetics
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Receptors, Thyroid Hormone / physiology*
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Transcription, Genetic
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Tuberous Sclerosis / genetics*
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Tuberous Sclerosis / physiopathology
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Tuberous Sclerosis Complex 1 Protein
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / physiology*
Substances
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IRS1 protein, human
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Insulin Receptor Substrate Proteins
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Phosphoproteins
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RORC protein, human
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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TSC1 protein, human
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TSC2 protein, human
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Tuberous Sclerosis Complex 1 Protein
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins