15 37

Cited 0 times in

Identification of MYC as an antinecroptotic protein that stifles RIPK1-RIPK3 complex formation

Authors
 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  ;  Sang Chul Lee  ;  Andrew Oberst  ;  Peter Vandenabeele  ;  Dong Hoon Shin  ;  Eun-Woo Lee  ;  Jaewhan Song 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.117(33) : 19982-19993, 2020-08 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2020-08
MeSH
Animals ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Leukemia / genetics ; Leukemia / metabolism* ; Leukemia / physiopathology ; Mice ; Mice, Inbred BALB C ; Necroptosis ; Protein Binding ; Protein Transport ; Proto-Oncogene Proteins c-myc / genetics ; Proto-Oncogene Proteins c-myc / metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinases / genetics ; Receptor-Interacting Protein Serine-Threonine Kinases / metabolism* ; Signal Transduction
Keywords
MYC ; RIPK3 ; TNF-α ; necroptosis
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.
Files in This Item:
T202003605.pdf Download
DOI
10.1073/pnas.2000979117
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Cheong, June-Won(정준원) ORCID logo https://orcid.org/0000-0002-1744-0921
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/180008
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links