c-myc Induces Autophagy in Rat 3Y1 Fibroblast Cells

Cell Structure and Function

Masayuki Nakajima⁶  Akitsugu Yamamoto³  Yoshie Takahashi⁴  Kenichiro Kosai¹  Hiroshi Kimura⁷  Makoto Tsuneoka⁷  Tsuyoshi Takahashi²  Toshiyuki Umata⁵  Yoshiro Koda⁷ 

[1] Department of Gene Therapy and Regenerative Medicine, Gifu University School of Medicine;Department of Microbiology, Fujita Health University, School of Medicine;Department of Bio-Science, Nagahama Institute of Bio-Science and Technology;Department of Dermatology, Kurume University School of Medicine;Radioisotope Research Center, University of Occupational and Environmental Health;Department of Pediatrics, Kurume University School of Medicine;Division of Human Genetics, Department of Forensic Medicine, Kurume University School of Medicine

关键词: autophagy;    apoptosis;    transformation;    myc;    mutant;    rat fibroblast;   

DOI  :  10.1247/csf.28.195

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(49)Cited-By(16)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.

【 授权许可】

Unknown