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.
Publisher
NATURE PUBLISHING GROUP
Issue Date
2007-04
Language
ENG
Keywords

PROTEIN-KINASES; CYCLE PROGRESSION; MAMMALIAN PROTEIN; RAPAMYCIN; YEAST; P70(S6K)/P85(S6K); DOWNSTREAM; DISRUPTION; ACTIVATION; INDUCTION

Citation

EMBO REPORTS, v.8, no.4, pp.360 - 365

ISSN
1469-221X
DOI
10.1038/sj.embor.7400917
URI
http://hdl.handle.net/10203/5480
Appears in Collection
BS-Journal Papers(저널논문)
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