Abstract
The tuberous sclerosis gene 2 product tuberin is an important regulator of the mammalian target of rapamycin (mTOR). In addition, tuberin is known to bind to the cyclin-dependent kinase (CDK) inhibitor p27(Kip1) (p27) and to regulate its stability and localization via mTOR-independent mechanisms. Recently, evidence has been provided that tuberin also affects p27 localization via regulating mTOR's potential to activate the serum- and glucocorticoid-inducible kinase (SGK1) to phosphorylate p27. Taken together, these findings strengthen the argument that besides mTOR-inhibitors, such as rapamycin analogues, p27 and CDKs could also be considered targets for hamartoma therapeutics in tuberous sclerosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
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Cyclin-Dependent Kinase Inhibitor p27 / physiology
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Cyclin-Dependent Kinases / metabolism*
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Cyclin-Dependent Kinases / physiology
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Humans
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Immunosuppressive Agents / therapeutic use*
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Intracellular Signaling Peptides and Proteins / physiology
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Phosphorylation
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Protein Serine-Threonine Kinases / physiology
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Sirolimus / therapeutic use*
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TOR Serine-Threonine Kinases
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Tuberous Sclerosis / drug therapy*
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Tuberous Sclerosis / metabolism
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Tuberous Sclerosis / physiopathology
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins / metabolism*
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Tumor Suppressor Proteins / physiology
Substances
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Immunosuppressive Agents
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Intracellular Signaling Peptides and Proteins
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TSC2 protein, human
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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MTOR protein, human
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Protein Serine-Threonine Kinases
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TOR Serine-Threonine Kinases
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Cyclin-Dependent Kinases
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Sirolimus