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PMID:23532117

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Citation

Shin, JH, Min, SH, Kim, SJ, Kim, YI, Park, J, Lee, HK and Yoo, OJ (2013) TAK1 regulates autophagic cell death by suppressing the phosphorylation of p70 S6 kinase 1. Sci Rep 3:1561

Abstract

There is growing interest in identifying regulators of autophagy. The molecular mechanism underlying transforming growth factor-β activated kinase 1 (TAK1)-induced autophagy is poorly understood. We found that TAK1 inhibits p70 S6 kinase1 (S6K1) phosphorylation by interfering interaction of raptor with S6K1, thus inducing autophagy. The factors that determine whether autophagy is cytoprotective or cytotoxic have not been fully elucidated. In Drosophila, TAK1 overexpression leads to an impaired eye phenotype despite inhibition of apoptosis, indicating that the phenotype was mainly due to autophagy. Also, TAK1 overexpression increases lactate dehydrogenase (LDH) level in mammalian cells. When treated with autophagy inhibitors, the level of TAK1-induced cytotoxicity or cell death was significantly attenuated, indicating that TAK1 induces cytotoxic autophagic cell death. This study provides the first in vitro and in vivo evidence of TAK1-induced autophagy and we believe that our findings significantly contribute to the understanding of the mechanisms underlying the induction of autophagy.

Links

PubMed PMC3609023 Online version:10.1038/srep01561

Keywords

Animals; Autophagy/physiology; Drosophila Proteins/metabolism; Drosophila melanogaster; HEK293 Cells; Humans; Intracellular Signaling Peptides and Proteins/metabolism; MAP Kinase Kinase Kinases/biosynthesis; MAP Kinase Kinase Kinases/metabolism; Phosphorylation; Ribosomal Protein S6 Kinases, 70-kDa/antagonists & inhibitors; Ribosomal Protein S6 Kinases, 70-kDa/metabolism; Starvation/physiopathology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:P91656

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0026323

F

Seeded From UniProt

complete

DROME:Q8SWT5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0026323

F

Seeded From UniProt

complete

DROME:Q94533

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0026323

F

Seeded From UniProt

complete

DROME:M3K7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

FB:FBgn0283472

F

Seeded From UniProt

complete

DROME:M3K7

involved_in

GO:0010506: regulation of autophagy

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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