c-myc induces autophagy in rat 3Y1 fibroblast cells.
The proto-oncogene c-myc is a multifunctional gene that regulates cell division, cell growth, and apoptosis. Here we report a new function of c-myc: induction of autophagy. Autophagy is a bulk degradation system for intracellular proteins. Autophagy proceeds with characteristic morphologies, which begins with the formation of a double-membrane structure called the autophagosome surrounding a portion of the cytoplasm, after which its outer membrane then fuses with the lysosomal membrane to become an autolysosome. Autophagosomes and autolysosomes are generally called autophagic vacuoles. When c-Myc protein was overexpressed in rat 3Y1 fibroblasts or when the chimeric protein c-MycER was activated by estrogen, the number of autophagic vacuoles in cells increased significantly. The formation of autophagic vacuoles induced by c-Myc was completely blocked by a specific inhibitor of autophagosome formation, 3-methyladenine. A c-Myc mutant lacking Myc Box II induced neither apoptosis nor oncogenic transformation, but still stimulated autophagy. An inhibitor of caspases suppressed apoptosis but not autophagy. These results suggest that the autophagy caused by c-myc is not due to the apoptosis or tumorigenesis induced by c-myc. Taken together, our results suggest that the induction of autophagy is a novel function of c-myc.
Tsuneoka
Makoto
M
Division of Human Genetics, Department of Forensic Medicine, Kurume University School of Medicine, Kurume, Japan. tsuneoka@med.kurume-u.ac.jp
Umata
Toshiyuki
T
Kimura
Hiroshi
H
Koda
Yoshiro
Y
Nakajima
Masayuki
M
Kosai
Kenichiro
K
Takahashi
Tsuyoshi
T
Takahashi
Yoshie
Y
Yamamoto
Akitsugu
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology*; D061945:Caspase Inhibitors; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004791:Enzyme Inhibitors / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D016259:Genes, myc; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins