期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 20, 期 23, 页码 8969-8982出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.20.23.8969-8982.2000
关键词
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资金
- NCI NIH HHS [R01 CA085912, R01CA85912] Funding Source: Medline
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 effecters of PTEN-mediated tumor suppression.
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