CDKs as therapeutic targets for the human genetic disease tuberous sclerosis?
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.
Rosner
M
M
Medical University of Vienna, Vienna, Austria.
Dolznig
H
H
Fuchs
C
C
Siegel
N
N
Valli
A
A
Hengstschläger
M
M
D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism* / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D020123:Sirolimus / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism* / Q000502:physiology
D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; D020123:Sirolimus