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

@article{citeulike:2310006, abstract = {Addgene: 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.}, address = {Department of Adult Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.}, author = {Nakamura, N. and Ramaswamy, S. and Vazquez, F. and Signoretti, S. and Loda, M. and Sellers, W. R. }, citeulike-article-id = {2310006}, issn = {0270-7306}, journal = {Mol Cell Biol}, keywords = {plasmid}, month = {December}, number = {23}, pages = {8969--8982}, posted-at = {2008-01-31 09:02:34}, priority = {2}, title = {Forkhead transcription factors are critical effectors of cell death and cell cycle arrest downstream of PTEN.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11073996}, volume = {20}, year = {2000} }

TY - JOUR ID - citeulike:2310006 L3 - citeulike-article-id:2310006 TI - Forkhead transcription factors are critical effectors of cell death and cell cycle arrest downstream of PTEN. JF - Mol Cell Biol VL - 20 IS - 23 SP - 8969 EP - 8982 AD - Department of Adult Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. SN - 0270-7306 N2 - Addgene: 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. KW - plasmid AU - Nakamura, N AU - Ramaswamy, S AU - Vazquez, F AU - Signoretti, S AU - Loda, M AU - Sellers, WR PY - 2000/12// UR - http://view.ncbi.nlm.nih.gov/pubmed/11073996 ER -