ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation

CMUR > College of Medicine > Graduate Institute of Cancer Biology > Journal articles > Item 310903500/7083

Please use this identifier to cite or link to this item: http://ir.cmu.edu.tw/ir/handle/310903500/7083

Title:	ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation
Authors:	(Jer-Yen Yang);(Cong S. Zong);(Weiya Xia);(Hirohito Yamaguchi);(Qingqing Ding);(Xiaoming Xie);(Jing-Yu Lang);賴建成(Chien-Chen Lai);(Chun-Ju Chang);黃偉謙(Wei-Chien Huang);(Hsin Huang);(Hsu-Ping Kuo);(Dung-Fang Lee);李龍緣(Long-Yuan Li);(Huang-Chun Lien);(Xiaoyun Cheng);(King-Jen Chang);(Chwan-Deng Hsiao);蔡輔仁(Fuu-Jen Tsai);蔡長海(Chang-Hai Tsai);(Aysegul A. Sahin);(William J. Muller);(Gordon B. Mills);(Dihua Yu);(Gabriel N. Hortobagyi);洪明奇(Mien-Chie Hung)*
Contributors:	醫學院癌症生物學研究所;中國附醫院長室
Date:	2008-02
Issue Date:	2009-08-26 16:11:23 (UTC+8)
Abstract:	補助或委託單位尚有 Breast Cancer Research Foundation Kadoorie Charitable Foundations? 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.
Relation:	NATURE CELL BIOLOGY 10(2)138~148
Appears in Collections:	[Graduate Institute of Cancer Biology] Journal articles

Files in This Item:

File	Size	Format
	0Kb	Unknown	444	View/Open

Loading...