ATG1, an autophagy regulator, inhibits cell growth by negatively regulating S6 kinase.
It has been proposed that cell growth and autophagy are coordinated in response to cellular nutrient status, but the relationship between them is not fully understood. Here, we have characterized the fly mutants of Autophagy-specific gene 1 (ATG1), an autophagy-regulating kinase, and found that ATG1 is a negative regulator of the target of rapamycin (TOR)/S6 kinase (S6K) pathway. Our Drosophila studies have shown that ATG1 inhibits TOR/S6K-dependent cell growth and development by interfering with S6K activation. Consistently, overexpression of ATG1 in mammalian cells also markedly inhibits S6K in a kinase activity-dependent manner, and short interfering RNA-mediated knockdown of ATG1 induces ectopic activation of S6K and S6 phosphorylation. Moreover, we demonstrated that ATG1 specifically inhibits S6K activity by blocking phosphorylation of S6K at Thr 389. Taken together, our genetic and biochemical results strongly indicate crosstalk between autophagy and cell growth regulation.
Lee
Sung Bae
SB
National Creative Research Initiatives Center for Cell Growth Regulation, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373-1 Kusong-dong, Yusong-gu, Taejon 305-701, Republic of Korea.
Kim
Sunhong
S
Lee
Jiwoon
J
Park
Jeehye
J
Lee
Gina
G
Kim
Yongsung
Y
Kim
Jin-Man
JM
Chung
Jongkyeong
J
D000818:Animals; D001343:Autophagy / Q000235:genetics*; D000071189:Autophagy-Related Protein-1 Homolog; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D013912:Threonine / Q000235:genetics / Q000378:metabolism
D000071189:Autophagy-Related Protein-1 Homolog; D029721:Drosophila Proteins; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D013912:Threonine; C416303:target of rapamycin protein, Drosophila; C518074:Atg1 protein, Drosophila