The HECTD3 E3 Ubiquitin Ligase Suppresses Cisplatin-Induced Apoptosis via Stabilizing MALT1

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	The HECTD3 E3 Ubiquitin Ligase Suppresses Cisplatin-Induced Apoptosis via Stabilizing MALT1
	Li Y 1,2; Chen X 1,3; Wang ZH 1; Zhao D 4; Chen H 5; Li HM 6,9; Chen CS[*]1
刊名	NEOPLASIA
	2013
卷号	15 期号:1 页码:39-48
通讯作者	chenc@mail.kiz.ac.cn
合作状况	其它
英文摘要	Homologous to the E6-associated protein carboxyl terminus domain containing 3 (HECTD3) is an E3 ubiquitin ligase with unknown functions. Here, we show that HECTD3 confers cancer cell resistance to cisplatin. To understand the molecular mechanisms, we performed a yeast two-hybrid analysis and identified mucosa-associated lymphoid tissue 1 (MALT1) as an HECTD3-interacting protein. HECTD3 promotes MALT1 ubiquitination with non-degradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it. HECTD3 depletion dramatically decreases the levels of MALT1 in MCF7 and HeLa cells treated with cisplatin, which is correlated to an increase in apoptosis. Knockdown of MALT1 likewise increases cisplatin-induced apoptosis in these cancer cells. However, HECTD3 overexpression leads to a decreased cisplatin-induced apoptosis, whereas overexpression of MALT1 partially rescues HECTD3 depletion-induced apoptosis. These findings suggest that HECTD3 promotes cell survival through stabilizing MALT1. Our data have important implications in cancer therapy by providing novel molecular targets.
收录类别	SCI
资助信息	This study was supported by the National Key Basic Research Program of China (No. 2013CB910900), National Nature Science Foundation of China (81072162, 81120108019, and U1132605), Top Talents Program of Yunnan Province, China (2010CI114) and National Cancer Institute (R01CA154625) to Junran Zhang.
语种	英语
WOS记录号	WOS:000318618200004
公开日期	2013-06-13
内容类型	期刊论文
源URL	[http://159.226.149.42:8088/handle/152453/7462]
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 & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China 2.State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 3.University of the Chinese Academy of Sciences, Beijing, China 4.The Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 5.Wadsworth Center, New York State Department of Health, Albany, NY 6.Cancer Hospital, Kunming Medical University, Kunming, Yunnan, China 7.SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY USA 8.Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH 9.Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, NY
推荐引用方式 GB/T 7714	Li Y,Chen X,Wang ZH,et al. The HECTD3 E3 Ubiquitin Ligase Suppresses Cisplatin-Induced Apoptosis via Stabilizing MALT1[J]. NEOPLASIA,2013,15(1):39-48.
APA	Li Y.,Chen X.,Wang ZH.,Zhao D.,Chen H.,...&Chen CS[*].(2013).The HECTD3 E3 Ubiquitin Ligase Suppresses Cisplatin-Induced Apoptosis via Stabilizing MALT1.NEOPLASIA,15(1),39-48.
MLA	Li Y,et al."The HECTD3 E3 Ubiquitin Ligase Suppresses Cisplatin-Induced Apoptosis via Stabilizing MALT1".NEOPLASIA 15.1(2013):39-48.