1. Identification of MYC as an antinecroptotic protein that stifles RIPK1–RIPK3 complex formation.
- Author
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Daehyeon Seong, Manhyung Jeong, Jinho Seo, Ji-Yoon Lee, Chi Hyun Hwang, Ho-Chul Shin, Jeong Yoon Shin, Young Woo Nam, Jeong Yeon Jo, Haeseung Lee, Hye-Jung Kim, Hwa-Ryeon Kim, Ji Hoon Oh, Sang-Jun Ha, Seung Jun Kim, Jae-Seok Roe, Wankyu Kim, June-Won Cheong, Kwang-Hee Bae, and Sang Chul Lee
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MYC proteins ,ONCOGENES ,TUMOR growth ,CYTOPLASM ,IDENTIFICATION - Abstract
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 path-way 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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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