Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
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.

http://www.ncbi.nlm.nih.gov/pubmed/11073996

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 RIS Download

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

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: R01CA85912

OMIM (Data, Gene Annotation)

Addgene (Reagent, Plasmid)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.