NEDD4L Protein Catalyzes Ubiquitination of PIK3CA Protein and Regulates   PI3K-AKT Signaling

doi:10.1074/jbc.M116.726083

CORC > 北京大学 > 生命科学学院

	NEDD4L Protein Catalyzes Ubiquitination of PIK3CA Protein and Regulates PI3K-AKT Signaling
	Wang, Zixi ; Dang, Tingting ; Liu, Tingting ; Chen, She ; Li, Lin ; Huang, Song ; Fang, Min
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2016
关键词	Akt PKB E3 ubiquitin ligase phosphatidylinositide 3-kinase (PI 3-kinase) proteasome protein degradation ubiquitylation (ubiquitination) NEDD4L PIK3CA LIGASE NEDD4L C2 DOMAIN T-CELLS CBL-B CANCER EXPRESSION MUTATIONS DEGRADATION PROGRESSION PROGNOSIS
DOI	10.1074/jbc.M116.726083
英文摘要	Oncogenic PIK3CA (p110), the catalytic subunit of class IA PI3K, plays a major role in PI3K-related cancer progression. The mechanisms underlying the dynamic regulation of PIK3CA protein levels remain unknown. Here we demonstrated that PIK3CA is regulated by polyubiquitination. We identified NEDD4L as the E3 ligase that catalyzes PIK3CA polyubiquitination, leading to its proteasome-dependent degradation. NEDD4L ubiquitinates both the free and regulatory subunit-bound PIK3CA but does not ubiquitinate the regulatory subunit of PI3K. Overexpression of NEDD4L accelerates the turnover rate of PIK3CA, whereas suppression of NEDD4L results in not only the accumulation of PIK3CA but also a paradoxical decrease of AKT activation. Thus, we propose that NEDD4L negatively regulates PIK3CA protein levels via ubiquitination and is required for the maintenance of PI3K-AKT signaling pathway.; National Basic Program of China 973 Program [2013CB910104]; National Natural Science Foundation of China [31271524]; start-up foundation from the Joint Center for Life Sciences at Peking University; post-doctoral fellowship from Joint Center for Life Sciences at Peking University; SCI(E); EI; PubMed; ARTICLE; min.fang@pku.edu.cn; 33; 17467-17477; 291
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/491627]
专题	生命科学学院
推荐引用方式 GB/T 7714	Wang, Zixi,Dang, Tingting,Liu, Tingting,et al. NEDD4L Protein Catalyzes Ubiquitination of PIK3CA Protein and Regulates PI3K-AKT Signaling[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2016.
APA	Wang, Zixi.,Dang, Tingting.,Liu, Tingting.,Chen, She.,Li, Lin.,...&Fang, Min.(2016).NEDD4L Protein Catalyzes Ubiquitination of PIK3CA Protein and Regulates PI3K-AKT Signaling.JOURNAL OF BIOLOGICAL CHEMISTRY.
MLA	Wang, Zixi,et al."NEDD4L Protein Catalyzes Ubiquitination of PIK3CA Protein and Regulates PI3K-AKT Signaling".JOURNAL OF BIOLOGICAL CHEMISTRY (2016).