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

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

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p27 / physiology
  • Cyclin-Dependent Kinases / metabolism*
  • Cyclin-Dependent Kinases / physiology
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Intracellular Signaling Peptides and Proteins / physiology
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / physiology
  • Sirolimus / therapeutic use*
  • TOR Serine-Threonine Kinases
  • Tuberous Sclerosis / drug therapy*
  • Tuberous Sclerosis / metabolism
  • Tuberous Sclerosis / physiopathology
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / metabolism*
  • Tumor Suppressor Proteins / physiology

Substances

  • Immunosuppressive Agents
  • Intracellular Signaling Peptides and Proteins
  • TSC2 protein, human
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Protein-Serine-Threonine Kinases
  • Cyclin-Dependent Kinases
  • Sirolimus