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USP33, a new player in lung cancer, mediates Slit-Robo signaling

ISSN号：1674-800X
期刊名称：Protein & Cell
时间：2014
页码：704-13
分类：Q782[生物学—分子生物学] TP242[自动化与计算机技术—控制科学与工程;自动化与计算机技术—检测技术与自动化装置]
作者机构：[1]State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China, [2]Department of Neurology, Center for Genetic Medicine, Lurie Cancer Center, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave., Chicago, IL 60611, USA, [3]Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China, [4]State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an 710032, China, [5]University of Chinese Academy of Sciences, Beijing 100049, China, [6]Department of Pathophysiology, Liaoning Medical University, Jinzhou 121001, China
相关基金：ACKNOWLEDGEMENTS We gratefully thank Dr. Zhipei Zhang for the assistance in lung cancers sample collection. We thank Mang Zheng for technical assistance. We thank other members of Wu lab for stimulating dis- cussion and helpful suggestions. This work was supported by the National Basic Research Program （973 Program）（2010CB529603 and 2013CB917803） and the National Natural Science Foundation of China （Grant No. 91132710）. RK was supported by China Post- doctoral Science Foundation （20110490615）. JYW is supported by NIH （Nos. RO1AG033004 and RO1CA175360）. JYW designed the study; PW, XC and RK performed the experiments and analyzed the data; XL, YN and KW provided tissue samples and important suggestions; LZ, JL and JYW supervised the experiments and analyzed the data; PW and JYW wrote the paper.
相关项目：情感和记忆神经环路与额颞叶痴呆

关键词：肺癌细胞, 机器人, 信号, 球员, 介导, 细胞迁移, 功能蛋白, 肿瘤抑制, USP33, Slit, Robo, lung cancer, Slit-Robosignaling, tumor suppressor, prognostic marker

中文摘要：

Ubiquitin 特定的朊酶(USP33 ) 33 是调整多样的细胞的过程的多功能的蛋白质。在肺癌症的 USP33 的表示和角色仍然保持未经勘探。在这研究，我们证明 USP33 在肺癌症病人的多重队是下面调整的， USP33 的那低表情与差的预后被联系。USP33 调停 Slit-Robo 在肺癌症房间移植发信号。USP33 的 Downregulation 在肺癌症房间减少 Robo1 的蛋白质稳定性，提供为在调停的 USP33 功能的以前未知的机制在肺癌症房间的裂缝活动。一起拿， USP33 是在调整 Slit-Robo 发信号的肺癌症的一个新播放器。我们的数据建议 USP33 可以作为一个预示的标记是为有潜力的肺癌症的候选人肿瘤 suppressor。

英文摘要：

Ubiquitin specific protease 33 （USP33） is a multifunctional protein regulating diverse cellular processes. The expression and role of USP33 in lung cancer remain unexplored. In this study, we show that USP33 is down-regulated in multi- ple cohorts of lung cancer patients and that low expression of USP33 is associated with poor prognosis. USP33 medi- ates Slit-Robo signaling in lung cancer cell migration. Downregulation of USP33 reduces the protein stability of Robol in lung cancer cells, providing a previously unknown mechanism for USP33 function in mediating Slit activity in lung cancer ceils. Taken together, USP33 is a new player in lung cancer that regulates Slit-Robo signaling. Our data suggest that USP33 may be a candidate tumor suppressor for lung cancer with potential as a prognostic marker.

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