PTEN induces cell cycle arrest by decreasing the level and nuclear localization of cyclin D1. Export

@article{citeulike:4680892, abstract = {PTEN is a tumor suppressor frequently inactivated in brain, prostate, and uterine cancers that acts as a phosphatase on phosphatidylinositol-3,4,5-trisphosphate, antagonizing the activity of the phosphatidylinositol 3'-OH kinase. PTEN manifests its tumor suppressor function in most tumor cells by inducing G(1)-phase cell cycle arrest. To study the mechanism of cell cycle arrest, we established a tetracycline-inducible expression system for PTEN in cell lines lacking this gene. Expression of wild-type PTEN but not of mutant forms unable to dephosphorylate phosphoinositides reduced the expression of cyclin D1. Cyclin D1 reduction was accompanied by a marked decrease in endogenous retinoblastoma (Rb) protein phosphorylation on cyclin D/CDK4-specific sites, showing an early negative effect of PTEN on Rb inactivation. PTEN expression also prevented cyclin D1 from localizing to the nucleus during the G(1)- to S-phase cell cycle transition. The PTEN-induced localization defect and the cell growth arrest could be rescued by the expression of a nucleus-persistent mutant form of cyclin D1, indicating that an important effect of PTEN is at the level of nuclear availability of cyclin D1. Constitutively active Akt/PKB kinase counteracted the effect of PTEN on cyclin D1 translocation. The data are consistent with an oncogenesis model in which a lack of PTEN fuels the cell cycle by increasing the nuclear availability of cyclin D1 through the Akt/PKB pathway.}, author = {Radu, A. and Neubauer, V. and Akagi, T. and Hanafusa, H. and Georgescu, M. M.}, citeulike-article-id = {4680892}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/12917336}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=12917336}, issn = {0270-7306}, journal = {Molecular and cellular biology}, keywords = {cell-culture, cyclin-d, proliferation, pten}, month = {September}, number = {17}, pages = {6139--6149}, posted-at = {2009-05-30 04:57:50}, priority = {2}, title = {PTEN induces cell cycle arrest by decreasing the level and nuclear localization of cyclin D1.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/12917336}, volume = {23}, year = {2003} }

TY - JOUR ID - citeulike:4680892 L3 - citeulike-article-id:4680892 N2 - PTEN is a tumor suppressor frequently inactivated in brain, prostate, and uterine cancers that acts as a phosphatase on phosphatidylinositol-3,4,5-trisphosphate, antagonizing the activity of the phosphatidylinositol 3'-OH kinase. PTEN manifests its tumor suppressor function in most tumor cells by inducing G(1)-phase cell cycle arrest. To study the mechanism of cell cycle arrest, we established a tetracycline-inducible expression system for PTEN in cell lines lacking this gene. Expression of wild-type PTEN but not of mutant forms unable to dephosphorylate phosphoinositides reduced the expression of cyclin D1. Cyclin D1 reduction was accompanied by a marked decrease in endogenous retinoblastoma (Rb) protein phosphorylation on cyclin D/CDK4-specific sites, showing an early negative effect of PTEN on Rb inactivation. PTEN expression also prevented cyclin D1 from localizing to the nucleus during the G(1)- to S-phase cell cycle transition. The PTEN-induced localization defect and the cell growth arrest could be rescued by the expression of a nucleus-persistent mutant form of cyclin D1, indicating that an important effect of PTEN is at the level of nuclear availability of cyclin D1. Constitutively active Akt/PKB kinase counteracted the effect of PTEN on cyclin D1 translocation. The data are consistent with an oncogenesis model in which a lack of PTEN fuels the cell cycle by increasing the nuclear availability of cyclin D1 through the Akt/PKB pathway. IS - 17 JF - Molecular and cellular biology SN - 0270-7306 EP - 6149 TI - PTEN induces cell cycle arrest by decreasing the level and nuclear localization of cyclin D1. VL - 23 SP - 6139 KW - cell-culture KW - cyclin-d KW - proliferation KW - pten AU - Radu, A AU - Neubauer, V AU - Akagi, T AU - Hanafusa, H AU - Georgescu, MM PY - 2003/09// UR - http://view.ncbi.nlm.nih.gov/pubmed/12917336 ER -