TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumorigenesis

CORC > 昆明动物研究所 > 昆明动物研究所 > 动物模型与人类重大疾病机理重点实验室 > 肿瘤生物学

	TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumorigenesis
	Zhao D 1,2; Zhi X 1,2; Zhou ZM 1; Chen CS[*]1
刊名	CARCINOGENESIS
	2012
卷号	33 期号:1 页码:59-67
通讯作者	chenc@mail.kiz.ac.cn
合作状况	其它
英文摘要	Kruppel-like factor 5 (KLF5) is a PY motif-containing transcription factor promoting breast cell proliferation. The KLF5 protein is rapidly degraded through the proteasome after ubiquitination by E3 ubiquitin ligases, such as WWP1 and SCF(Fbw7). In this study, we demonstrated that a transcriptional co-activator with the PDZ-binding motif (TAZ) upregulated the KLF5 expression through antagonizing the WWP1-, but not Fbw7-, mediated KLF5 ubiquitination and degradation. TAZ interacted with KLF5 through the WW domain of TAZ and the PY motif of KLF5, which is the binding site for WWP1. TAZ inhibited WWP1-KLF5 protein interaction and WWP1-mediated KLF5 ubiquitination and degradation in a WW domain-dependent manner. Overexpression of TAZ upregulated the protein levels of KLF5 and FGF-BP, which is a well-established KLF5 target gene. In addition, depletion of TAZ in both 184A1 and HCC1937 breast cells downregulated protein levels of KLF5 and FGF-BP and inhibited cell growth. Furthermore, stable depletion of either TAZ or KLF5 significantly suppressed HCC1937 xenograft growth in immunodeficient mice. Knockdown of LATS1, a TAZ upstream inhibitory kinase, up-regulated the protein levels of KLF5 and FGF-BP in 184A1 and promoted cell growth through TAZ. Finally, both KLF5 and TAZ were co-expressed in a subset of estrogen receptor alpha-negative breast cell lines. These results, for the first time, suggest that TAZ promotes breast cell growth partially through protecting KLF5 from WWP1-mediated degradation and enhancing KLF5's activities
收录类别	SCI
资助信息	National Nature Science Foundation of China (81072162, 81120108019, U1132605); Yunnan Province High-Profile Scientist Program (2010CI114).
语种	英语
WOS记录号	WOS:000298659200008
公开日期	2012-03-20
内容类型	期刊论文
源URL	[http://159.226.149.42:8088/handle/353002/6899]
专题	昆明动物研究所_肿瘤生物学昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位	1.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China 2.The Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA
推荐引用方式 GB/T 7714	Zhao D,Zhi X,Zhou ZM,et al. TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumorigenesis[J]. CARCINOGENESIS,2012,33(1):59-67.
APA	Zhao D,Zhi X,Zhou ZM,&Chen CS[*].(2012).TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumorigenesis.CARCINOGENESIS,33(1),59-67.
MLA	Zhao D,et al."TAZ antagonizes the WWP1-mediated KLF5 degradation and promotes breast cell proliferation and tumorigenesis".CARCINOGENESIS 33.1(2012):59-67.