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学科主题: 基础医学
题名:
Protein kinase D1 is essential for Ras-induced senescence and tumor suppression by regulating senescence-associated inflammation
作者: Wang, Pan1,2; Han, Limin1,2; Shen, Hong1,2; Wang, Pengfeng1,2; Lv, Cuicui1,2; Zhao, Ganye1,2; Niu, Jing3; Xue, Lixiang1,2; Wang, Qiming Jane4; Tong, Tanjun1,2; Chen, Jun1,2
刊名: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
发表日期: 2014-05-27
DOI: 10.1073/pnas.1310972111
卷: 111, 期:21, 页:7683-7688
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: ONCOGENE-INDUCED SENESCENCE ; NF-KAPPA-B ; CELLULAR SENESCENCE ; OXIDATIVE STRESS ; GASTRIC-CANCER ; ACTIVATION ; PATHWAY ; CELLS ; EXPRESSION ; INVASION
英文摘要:

Oncogene-induced senescence (OIS) is an initial barrier to tumor development. Reactive oxygen species (ROS) is critical for oncogenic Ras OIS, but the downstream effectors to mediate ROS signaling are still relatively elusive. Senescent cells develop a senescence-associated secretory phenotype (SASP). However, the mechanisms underlying the regulation of the SASP are largely unknown. Here, we identify protein kinase D1 (PKD1) as a downstream effector of ROS signaling to mediate Ras OIS and SASP. PKD1 is activated by oncogenic Ras expression and PKD1 promotes Ras OIS by mediating inflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8) via modulation of NF-kappa B activity. We demonstrate that ROS-protein kinase C delta (PKC delta)-PKD1 axis is essential for the establishment and maintenance of IL-6/IL8 induction. In addition, ablation of PKD1 causes the bypass of Ras OIS, and promotes cell transformation and tumorigenesis. Together, these findings uncover a previously unidentified role of ROS-PKC delta-PKD1 pathway in Ras OIS and SASP regulation.

语种: 英语
所属项目编号: 2013CB530801 ; 2014CB910503 ; 81370455
项目资助者: National Key Basic Research Program of China ; National Natural Science Foundation of China
WOS记录号: WOS:000336411300047
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59841
Appears in Collections:基础医学院_北京大学衰老研究中心_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Res Ctr Aging, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
3.Capital Med Univ, Dept Biochem & Mol Biol, Beijing 100069, Peoples R China
4.Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA

Recommended Citation:
Wang, Pan,Han, Limin,Shen, Hong,et al. Protein kinase D1 is essential for Ras-induced senescence and tumor suppression by regulating senescence-associated inflammation[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2014,111(21):7683-7688.
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