ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer
文献类型：期刊论文
| 作者 | Ji, SR; Qin, Y; Shi, S; Liu, XY; Hu, HL; Zhou, H; Gao, J; Zhang, B; Xu, WY; Liu, J |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2015 |
| 卷号 | 25期号:5页码:561-573 |
| 关键词 | KRAS pancreatic cancer ERK FBW7 |
| 通讯作者 | Yu, XJ (reprint author), Fudan Univ, Shanghai Canc Ctr, Dept Pancreat & Hepatobiliary Surg, Shanghai 200032, Peoples R China.,yuxianjun@fudan.edu.cn |
| 英文摘要 | F-box and WD repeat domain-containing 7 (FBW7) is the substrate recognition component of the Skp1-Cul1-Fbox (SCF) ubiquitin ligase complex and functions as a major tumor suppressor by targeting various oncoproteins for degradation. Genomic deletion or mutation of FBW7 has frequently been identified in many human cancers but not in pancreatic ductal adenocarcinoma. Thus it is important to know how the tumor suppressive function of FBW7 is impaired in pancreatic cancer. In this study, we first observed that low FBW7 expression correlated significantly with ERK activation in pancreatic cancer clinical samples, primarily due to KRAS mutations in pancreatic cancer. We further showed that ERK directly interacted with FBW7 and phosphorylated FBW7 at Thr205, which sequentially promoted FBW7 ubiquitination and proteasomal degradation. Furthermore, the phospho-deficient T205A FBW7 mutant is resistant to ERK activation and could significantly suppress pancreatic cancer cell proliferation and tumorigenesis. These results collectively demonstrate how the oncogenic KRAS mutation inhibits the tumor suppressor FBW7, thus revealing an important function of KRAS mutations in promoting pancreatic cancer progression. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | F-BOX PROTEIN ; UBIQUITIN LIGASE ; C-MYC ; FBXW7 EXPRESSION ; POOR-PROGNOSIS ; MOUSE MODELS ; CYCLIN-E ; DEGRADATION ; DESTRUCTION ; PATHWAY |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000353917500008 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/68]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Ji, SR,Qin, Y,Shi, S,et al. ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer[J]. CELL RESEARCH,2015,25(5):561-573. |
| APA | Ji, SR.,Qin, Y.,Shi, S.,Liu, XY.,Hu, HL.,...&Yu, XJ.(2015).ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer.CELL RESEARCH,25(5),561-573. |
| MLA | Ji, SR,et al."ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer".CELL RESEARCH 25.5(2015):561-573. |
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