PTK2-mediated degradation of ATG3 impedes cancer cells susceptible to   DNA damage treatment

doi:10.1080/15548627.2016.1272742

CORC > 北京大学 > 生命科学学院

	PTK2-mediated degradation of ATG3 impedes cancer cells susceptible to DNA damage treatment
	Ma, Ke ; Fu, Wan ; Tang, Ming ; Zhang, Chaohua ; Hou, Tianyun ; Li, Ran ; Lu, Xiaopeng ; Wang, Yanan ; Zhou, Jingyi ; Li, Xue ; Zhang, Luyao ; Wang, Lina ; Zhao, Ying ; Zhu, Wei-Guo
刊名	AUTOPHAGY
	2017
关键词	ATG3 cancer therapy mitotic catastrophe PTK2 tyrosine phosphorylation FOCAL ADHESION KINASE MITOTIC CATASTROPHE AUTOPHAGOSOME FORMATION OVARIAN-CANCER TUMOR-GROWTH FAK CONJUGATION CARCINOMA PATHWAYS DEATH
DOI	10.1080/15548627.2016.1272742
英文摘要	ATG3 (autophagy-related 3) is an E2-like enzyme essential for autophagy; however, it is unknown whether it has an autophagy-independent function. Here, we report that ATG3 is a relatively stable protein in unstressed cells, but it is degraded in response to DNA-damaging agents such as etoposide or cisplatin. With mass spectrometry and a mutagenesis assay, phosphorylation of tyrosine 203 of ATG3 was identified to be a critical modification for its degradation, which was further confirmed by manipulating ATG3(Y203E) (phosphorylation mimic) or ATG3(Y203F) (phosphorylation-incompetent) in Atg3 knockout MEFs. In addition, by using a generated phospho-specific antibody we showed that phosphorylation of Y203 significantly increased upon etoposide treatment. With a specific inhibitor or siRNA, PTK2 (protein tyrosine kinase 2) was confirmed to catalyze the phosphorylation of ATG3 at Y203. Furthermore, a newly identified function of ATG3 was recognized to be associated with the promotion of DNA damage-induced mitotic catastrophe, in which ATG3 interferes with the function of BAG3, a crucial protein in the mitotic process, by binding. Finally, PTK2 inhibition-induced sustained levels of ATG3 were able to sensitize cancer cells to DNA-damaging agents. Our findings strengthen the notion that targeting PTK2 in combination with DNA-damaging agents is a novel strategy for cancer therapy.; National Natural Science Foundation of China [31570812, 81222028, 81321003, 81472581, 81530074, 81672712, 91319302, 31261140372]; Discipline Construction Funding of Shenzhen; Shenzhen Municipal Commission of Science and Technology Innovation [JCYJ20160427104855100]; SCI(E); ARTICLE; 3; 579-591; 13
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/476203]
专题	生命科学学院
推荐引用方式 GB/T 7714	Ma, Ke,Fu, Wan,Tang, Ming,et al. PTK2-mediated degradation of ATG3 impedes cancer cells susceptible to DNA damage treatment[J]. AUTOPHAGY,2017.
APA	Ma, Ke.,Fu, Wan.,Tang, Ming.,Zhang, Chaohua.,Hou, Tianyun.,...&Zhu, Wei-Guo.(2017).PTK2-mediated degradation of ATG3 impedes cancer cells susceptible to DNA damage treatment.AUTOPHAGY.
MLA	Ma, Ke,et al."PTK2-mediated degradation of ATG3 impedes cancer cells susceptible to DNA damage treatment".AUTOPHAGY (2017).