Dual function of partitioning-defective 3 in the regulation of YAP phosphorylation and activation

doi:10.1038/celldisc.2016.21

	Dual function of partitioning-defective 3 in the regulation of YAP phosphorylation and activation
	Zhang, Peng 1,2; Wang, Shuting 1,2; Wang, Sai 1,2; Qiao, Jing 1,2; Zhang, Lei 3; Zhang, Zhe 1; Chen, Zhengjun1,4
	2016-07-05
发表期刊	CELL DISCOVERY
ISSN	2056-5968
卷号	2
发表状态	已发表
DOI	10.1038/celldisc.2016.21
摘要	Partitioning-defective 3 (Par3), a key component of the evolutionarily conserved polarity PAR complex (Par3/Par6/aPKC), controls cell polarity and contributes to cell migration, proliferation and tumor development. Emerging evidence indicates that cell polarity proteins function as upstream modulators that regulate the Hippo pathway. However, little is known about Par3's involvement in the Hippo pathway. Here, we find Par3 and YAP dynamically co-localize in different subcellular compartments; that is, the membrane, cytoplasm and nucleus, in a cell-density-dependent manner. Interestingly, Par3 knockdown promotes YAP phosphorylation, leading to a significant impairment of YAP nuclear translocation at low cell density, but not at high density, in MDCK cells. Furthermore, via its third PDZ domain, Par3 directly binds to the PDZ-binding motif of YAP. The interaction is required for regulating YAP phosphorylation and nuclear localization. Mechanistically, Par3, as a scaffold protein, associates with LATS1 and protein phosphatase 1, a subunit (PP1A) in the cytoplasm and nucleus. Par3 promotes the dephosphorylation of LATS1 and YAP, thus enhancing YAP activation and cell proliferation. Strikingly, we also find that under the condition of PP1A knockdown, Par3 expression promotes YAP hyperphosphorylation, leading to the suppression of YAP activity and its downstream targets. Par3 expression results in differential effects on YAP phosphorylation and activation in different tumor cell lines. These findings indicate that Par3 may have a dual role in regulating the activation of the Hippo pathway, in a manner possibly dependent on cellular context or cell type in response to cell-cell contact and cell polarity signals.
关键词	LATS1 Par3 PP1A YAP
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[31430055] ; National Natural Science Foundation of China[31190062] ; National Natural Science Foundation of China[31170723]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000414804000001
出版者	NATURE PUBLISHING GROUP
WOS关键词	EPITHELIAL-CELL POLARITY ; ORGAN SIZE CONTROL ; PROTEIN-KINASE-C ; HIPPO PATHWAY ; NUCLEAR-LOCALIZATION ; CONTACT INHIBITION ; COMPLEX ; PAR-3 ; DROSOPHILA ; CARCINOMA
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/10024
专题	生命科学与技术学院_特聘教授组_陈正军组
通讯作者	Chen, Zhengjun
作者单位	1.Chinese Acad Sci, Key Lab Syst Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Chinese Acad Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zhang, Peng,Wang, Shuting,Wang, Sai,et al. Dual function of partitioning-defective 3 in the regulation of YAP phosphorylation and activation[J]. CELL DISCOVERY,2016,2.
APA	Zhang, Peng.,Wang, Shuting.,Wang, Sai.,Qiao, Jing.,Zhang, Lei.,...&Chen, Zhengjun.(2016).Dual function of partitioning-defective 3 in the regulation of YAP phosphorylation and activation.CELL DISCOVERY,2.
MLA	Zhang, Peng,et al."Dual function of partitioning-defective 3 in the regulation of YAP phosphorylation and activation".CELL DISCOVERY 2(2016).