期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 33, 页码 19982-19993出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2000979117
关键词
MYC; RIPK3; TNF-alpha; necroptosis
资金
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2015R1A3A2066581]
- Brain Korea 21 (BK21) PLUS program
- Basic Science Research Program through the NRF - Ministry of Education [NRF-2019R1C1C1002831]
- Korea Research Institute of Bioscience and Biotechnology Research Initiative Program
- Graduate School of Yonsei University
- National Cancer Center [1710080]
- NRF [NRF-2017M3A9F9030648]
- Flemish grants (EOS MODEL-IDI consortium) [G.0C31.14N, G.0C37.14N, G.0E04.16N, G.0C76.18N, G.0B71.18N]
- Methusalem [BOF16/MET_V/007]
- Foundation against Cancer [FAF-F/2016/865]
- Vlaams Instituut voor Biotechnologie
The underlying mechanism of necroptosis in relation to cancer is still unclear. Here, MYC, a potent oncogene, is an antinecroptotic factor that directly suppresses the formation of the RIPK1-RIPK3 complex. Gene set enrichment analyses reveal that the MYC pathway is the most prominently down-regulated signaling pathway during necroptosis. Depletion or deletion of MYC promotes the RIPK1-RIPK3 interaction, thereby stabilizing the RIPK1 and RIPK3 proteins and facilitating necroptosis. Interestingly, MYC binds to RIPK3 in the cytoplasm and inhibits the interaction between RIPK1 and RIPK3 in vitro. Furthermore, MYC-nick, a truncated form that is mainly localized in the cytoplasm, prevented TNF-induced necroptosis. Finally, down-regulation of MYC enhances necroptosis in leukemia cells and suppresses tumor growth in a xenograft model upon treatment with birinapant and emricasan. MYC-mediated suppression of necroptosis is a mechanism of necroptosis resistance in cancer, and approaches targeting MYC to induce necroptosis represent an attractive therapeutic strategy for cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据