Myc inhibits JNK-mediated cell death in vivo

Jiuhong Huang; Yu Feng; Xinhong Chen; Wenzhe Li; Lei Xue

doi:10.1007/s10495-016-1340-4

Myc inhibits JNK-mediated cell death in vivo

Apoptosis. 2017 Apr;22(4):479-490. doi: 10.1007/s10495-016-1340-4.

Authors

Jiuhong Huang¹, Yu Feng¹, Xinhong Chen¹, Wenzhe Li², Lei Xue³

Affiliations

¹ Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.
² Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China. [email protected].
³ Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China. [email protected].

PMID: 28150056
DOI: 10.1007/s10495-016-1340-4

Abstract

The proto-oncogene Myc is well known for its roles in promoting cell growth, proliferation and apoptosis. However, in this study, we found from a genetic screen that Myc inhibits, rather than promotes, cell death triggered by c-Jun N-terminal kinase (JNK) signaling in Drosophila. Firstly, expression of Drosophila Myc (dMyc) suppresses, whereas loss of dMyc enhances, ectopically activated JNK signaling-induced cell death. Secondly, dMyc impedes physiologically activated JNK pathway-mediated cell death. Thirdly, loss of dMyc triggers JNK pathway activation and JNK-dependent cell death. Finally, the mammalian cMyc gene, when expressed in Drosophila, impedes activated JNK signaling-induced cell death. Thus, besides its well-studied apoptosis promoting function, Myc also antagonizes JNK-mediated cell death in Drosophila, and this function is likely conserved from fly to human.

Keywords: Cell death; Drosophila; JNK pathway; Myc.

MeSH terms

Animals
Apoptosis / genetics*
Compound Eye, Arthropod / cytology
Compound Eye, Arthropod / embryology
Compound Eye, Arthropod / growth & development
DNA-Binding Proteins / deficiency
DNA-Binding Proteins / genetics
DNA-Binding Proteins / physiology*
Drosophila Proteins / deficiency
Drosophila Proteins / genetics
Drosophila Proteins / physiology*
Drosophila melanogaster / cytology
Drosophila melanogaster / genetics*
Female
Gene Expression Regulation, Developmental
Genes, Synthetic
Genes, myc*
Humans
Larva
MAP Kinase Signaling System / genetics*
Membrane Proteins / genetics
Membrane Proteins / physiology
Morphogenesis
Protein Isoforms / genetics
Protein Isoforms / physiology
Proto-Oncogene Mas
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / physiology
Recombinant Fusion Proteins / metabolism
Species Specificity
Thorax / cytology
Thorax / embryology
Thorax / growth & development
Transcription Factors / deficiency
Transcription Factors / genetics
Transcription Factors / physiology*
Wings, Animal / cytology
Wings, Animal / embryology
Wings, Animal / growth & development

Substances

DNA-Binding Proteins
Drosophila Proteins
GAL4 protein, Drosophila
MAS1 protein, human
MYC protein, human
Membrane Proteins
Myc protein, Drosophila
Protein Isoforms
Proto-Oncogene Mas
Proto-Oncogene Proteins c-myc
Recombinant Fusion Proteins
Transcription Factors
egr protein, Drosophila