ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation.

@article{citeulike:2294883, abstract = {The RAS-ERK pathway is known to play a pivotal role in differentiation, proliferation and tumour progression. Here, we show that Erk downregulates Forkhead box O 3a (FOXO3a) by directly interacting with and phosphorylating FOXO3a at Ser 294, Ser 344 and Ser 425, which consequently promotes cell proliferation and tumorigenesis. The ERK-phosphorylated FOXO3a degrades via an MDM2-mediated ubiquitin-proteasome pathway. However, the non-phosphorylated FOXO3a mutant is resistant to the interaction and degradation by murine double minute 2 (MDM2), thereby resulting in a strong inhibition of cell proliferation and tumorigenicity. Taken together, our study elucidates a novel pathway in cell growth and tumorigenesis through negative regulation of FOXO3a by RAS-ERK and MDM2.}, address = {[1] Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas, Houston, TX 77030, USA.}, author = {Yang, Jer-Yen Y. and Zong, Cong S S. and Xia, Weiya and Yamaguchi, Hirohito and Ding, Qingqing and Xie, Xiaoming and Lang, Jing-Yu Y. and Lai, Chien-Chen C. and Chang, Chun-Ju J. and Huang, Wei-Chien C. and Huang, Hsin and Kuo, Hsu-Ping P. and Lee, Dung-Fang F. and Li, Long-Yuan Y. and Lien, Huang-Chun C. and Cheng, Xiaoyun and Chang, King-Jen J. and Hsiao, Chwan-Deng D. and Tsai, Fuu-Jen J. and Tsai, Chang-Hai H. and Sahin, Aysegul A A. and Muller, William J J. and Mills, Gordon B B. and Yu, Dihua and Hortobagyi, Gabriel N N. and Hung, Mien-Chie C. }, citeulike-article-id = {2294883}, doi = {http://dx.doi.org/10.1038/ncb1676}, issn = {1465-7392}, journal = {Nat Cell Biol}, keywords = {example, peptides}, month = {January}, posted-at = {2008-05-30 14:39:46}, priority = {2}, title = {ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation.}, url = {http://dx.doi.org/10.1038/ncb1676}, year = {2008} }

TY - JOUR ID - citeulike:2294883 L3 - citeulike-article-id:2294883 TI - ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation. JF - Nat Cell Biol AD - [1] Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. [2] Graduate School of Biomedical Sciences, The University of Texas, Houston, TX 77030, USA. SN - 1465-7392 N2 - The RAS-ERK pathway is known to play a pivotal role in differentiation, proliferation and tumour progression. Here, we show that Erk downregulates Forkhead box O 3a (FOXO3a) by directly interacting with and phosphorylating FOXO3a at Ser 294, Ser 344 and Ser 425, which consequently promotes cell proliferation and tumorigenesis. The ERK-phosphorylated FOXO3a degrades via an MDM2-mediated ubiquitin-proteasome pathway. However, the non-phosphorylated FOXO3a mutant is resistant to the interaction and degradation by murine double minute 2 (MDM2), thereby resulting in a strong inhibition of cell proliferation and tumorigenicity. Taken together, our study elucidates a novel pathway in cell growth and tumorigenesis through negative regulation of FOXO3a by RAS-ERK and MDM2. KW - example KW - peptides AU - Yang, Jer-Yen AU - Zong, Cong S AU - Xia, Weiya AU - Yamaguchi, Hirohito AU - Ding, Qingqing AU - Xie, Xiaoming AU - Lang, Jing-Yu AU - Lai, Chien-Chen AU - Chang, Chun-Ju AU - Huang, Wei-Chien AU - Huang, Hsin AU - Kuo, Hsu-Ping AU - Lee, Dung-Fang AU - Li, Long-Yuan AU - Lien, Huang-Chun AU - Cheng, Xiaoyun AU - Chang, King-Jen AU - Hsiao, Chwan-Deng AU - Tsai, Fuu-Jen AU - Tsai, Chang-Hai AU - Sahin, Aysegul A AU - Muller, William J AU - Mills, Gordon B AU - Yu, Dihua AU - Hortobagyi, Gabriel N AU - Hung, Mien-Chie PY - 2008/01/20/ UR - http://dx.doi.org/10.1038/ncb1676 ER -