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CDKs as therapeutic targets for the human genetic disease tuberous sclerosis?
Author(s) -
Rosner M.,
Dolznig H.,
Fuchs C.,
Siegel N.,
Valli A.,
Hengstschläger M.
Publication year - 2009
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2009.02213.x
Subject(s) - tuberous sclerosis , pi3k/akt/mtor pathway , cyclin dependent kinase , rptor , regulator , tsc1 , mtorc1 , tsc2 , cancer research , sirolimus , kinase , sgk1 , microbiology and biotechnology , biology , cyclin , gene , signal transduction , medicine , cell cycle , genetics , biochemistry , pathology
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.