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ATG1, an autophagy regulator, inhibits cell growth by negatively regulating S6 kinase
Author(s) -
Lee Sung Bae,
Kim Sunhong,
Lee Jiwoon,
Park Jeehye,
Lee Gina,
Kim Yongsung,
Kim JinMan,
Chung Jongkyeong
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400917
Subject(s) - p70 s6 kinase 1 , tor signaling , autophagy , microbiology and biotechnology , biology , gene knockdown , crosstalk , regulator , kinase , phosphorylation , cell growth , ectopic expression , gene , apoptosis , biochemistry , protein kinase b , physics , optics
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.