Preparing your results

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Forkhead transcription factors are critical effectors of cell death and cell cycle arrest downstream of PTEN.

PTEN acts as a tumor suppressor, at least in part, by antagonizing phosphoinositide 3-kinase (PI3K)/Akt signaling. Here we show that Forkhead transcription factors FKHRL1 and FKHR, substrates of the Akt kinase, are aberrantly localized to the cytoplasm and cannot activate transcription in PTEN-deficient cells. Restoration of PTEN function restores FKHR to the nucleus and restores transcriptional activation. Expression of a constitutively active form of FKHR that cannot be phosphorylated by Akt produces the same effect as reconstitution of PTEN on PTEN-deficient tumor cells. Specifically, activated FKHR induces apoptosis in cells that undergo PTEN-mediated cell death and induces G(1) arrest in cells that undergo PTEN-mediated cell cycle arrest. Furthermore, both PTEN and constitutively active FKHR induce p27(KIP1) protein but not p21. These data suggest that Forkhead transcription factors are critical effectors of PTEN-mediated tumor suppression.

Pubmed ID: 11073996


  • Nakamura N
  • Ramaswamy S
  • Vazquez F
  • Signoretti S
  • Loda M
  • Sellers WR


Molecular and cellular biology

Publication Data

December 19, 2000

Associated Grants

  • Agency: NCI NIH HHS, Id: R01CA85912

Mesh Terms

  • Biological Transport
  • Cell Compartmentation
  • Cell Cycle
  • Cell Cycle Proteins
  • Cell Death
  • Cell Nucleus
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases
  • DNA-Binding Proteins
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Half-Life
  • Microtubule-Associated Proteins
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases
  • Phosphorylation
  • Signal Transduction
  • Transcription Factors
  • Transcription, Genetic
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins