1. CDKs as therapeutic targets for the human genetic disease tuberous sclerosis?
- Author
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Nicol Siegel, Marsha Rich Rosner, Christiane Fuchs, Markus Hengstschläger, Alessandro Valli, and Helmut Dolznig
- Subjects
biology ,Clinical Biochemistry ,RPTOR ,General Medicine ,medicine.disease ,Biochemistry ,Tuberous sclerosis protein ,Tuberous sclerosis ,Cyclin-dependent kinase ,Sirolimus ,medicine ,biology.protein ,SGK1 ,Cancer research ,TOR Serine-Threonine Kinases ,PI3K/AKT/mTOR pathway ,medicine.drug - 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.
- Published
- 2009
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