Cited 13 time in
- Identification of MYC as an antinecroptotic protein that stifles RIPK1-RIPK3 complex formation
- D Seong; M Jeong; Jinho Seo; Ji-Yoon Lee; C H Hwang; Ho Chul Shin; J Y Shin; Y W Nam; J Y Jo; H Lee; H J Kim; H R Kim; J H Oh; S J Ha; Seung Jun Kim; J S Roe; W Kim; J W Cheong; Kwang-Hee Bae; Sang Chul Lee; A Oberst; P Vandenabeele; D H Shin; Eun-Woo Lee; J Song
- Bibliographic Citation
- Proceedings of National Academy of Sciences of United States of America, vol. 117, no. 33, pp. 19982-19993
- Publication Year
- 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.
- Natl Acad Sciences
- Appears in Collections:
- Aging Convergence Research Center > 1. Journal Articles
Critical Diseases Diagnostics Convergence Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
- Files in This Item:
Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.