Methionine restriction breaks obligatory coupling of cell proliferation and death by an oncogene src in drosophila

Hiroshi Nishida, Morihiro Okada, Lynna Yang, Tomomi Takano, Sho Tabata, Tomoyoshi Soga, Diana M. Ho, Jongkyeong Chung, Yasuhiro Minami, Sa Kan Yoo

Research output: Contribution to journalArticlepeer-review

Abstract

Oncogenes often promote cell death as well as proliferation. How oncogenes drive these diametrically opposed phenomena remains to be solved. A key question is whether cell death occurs as a response to aberrant proliferation signals or through a proliferation-independent mechanism. Here, we reveal that Src, the first identified oncogene, simultaneously drives cell proliferation and death in an obligatorily coupled manner through parallel MAPK pathways. The two MAPK pathways diverge from a lynchpin protein Slpr. A MAPK p38 drives proliferation whereas another MAPK JNK drives apoptosis independently of proliferation signals. Src-p38induced proliferation is regulated by methionine-mediated Tor signaling. Reduction of dietary methionine uncouples the obligatory coupling of cell proliferation and death, suppressing tumorigenesis and tumor-induced lethality. Our findings provide an insight into how cells evolved to have a fail-safe mechanism that thwarts tumorigenesis by the oncogene Src. We also exemplify a diet-based approach to circumvent oncogenesis by exploiting the fail-safe mechanism.

Original languageEnglish
Article numbere59809
JournaleLife
Volume10
DOIs
Publication statusPublished - 2021

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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