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Eur J Clin Invest. 2009 Dec;39(12):1033-5. doi: 10.1111/j.1365-2362.2009.02213.x. Epub 2009 Sep 9.

CDKs as therapeutic targets for the human genetic disease tuberous sclerosis?

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Medical University of Vienna, Vienna, Austria.


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.

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