学科主题基础医学
Protein kinase D1 is essential for Ras-induced senescence and tumor suppression by regulating senescence-associated inflammation
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
2014-05-27
DOI10.1073/pnas.1310972111
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
WOS记录号WOS:000336411300047
项目编号2013CB530801 ; 2014CB910503 ; 81370455
资助机构National Key Basic Research Program of China ; National Natural Science Foundation of China
引用统计
被引频次:22[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59841
专题北京大学基础医学院_北京大学衰老研究中心
北京大学基础医学院
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
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GB/T 7714
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.
APA Wang, Pan.,Han, Limin.,Shen, Hong.,Wang, Pengfeng.,Lv, Cuicui.,...&Chen, Jun.(2014).Protein kinase D1 is essential for Ras-induced senescence and tumor suppression by regulating senescence-associated inflammation.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,111(21),7683-7688.
MLA Wang, Pan,et al."Protein kinase D1 is essential for Ras-induced senescence and tumor suppression by regulating senescence-associated inflammation".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 111.21(2014):7683-7688.
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