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Identification of MYC as an antinecroptotic protein that stifles RIPK1-RIPK3 complex formation
- Title
- Identification of MYC as an antinecroptotic protein that stifles RIPK1-RIPK3 complex formation
- Authors
- Seong, Daehyeon; Jeong, Manhyung; Seo, Jinho; Lee, Ji-Yoon; Hwang, Chi Hyun; Shin, Ho-Chul; Shin, Jeong Yoon; Nam, Young Woo; Jo, Jeong Yeon; Lee, Haeseung; Kim, Hye-Jung; Kim, Hwa-Ryeon; Oh, Ji Hoon; Ha, Sang-Jun; Kim, Seung Jun; Roe, Jae-Seok; Kim, Wankyu; Cheong, June-Won; Bae, Kwang-Hee; Lee, Sang Chul; Oberst, Andrew; Vandenabeele, Peter; Shin, Dong Hoon; Lee, Eun-Woo; Song, Jaewhan
- Ewha Authors
- 김완규
- SCOPUS Author ID
- 김완규
- Issue Date
- 2020
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- ISSN
- 0027-8424
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA vol. 117, no. 33, pp. 19982 - 19993
- Keywords
- MYC; RIPK3; TNF-alpha; necroptosis
- Publisher
- NATL ACAD SCIENCES
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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 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.
- DOI
- 10.1073/pnas.2000979117
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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