TAK1 regulates autophagic cell death by suppressing the phosphorylation of p70 S6 kinase 1

Ju Hyun Shin, Sang Hyun Min, Seong Jin Kim, Young Il Kim, Junsoo Park, Heung Kyu Lee, Ook Joon Yoo

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36 Citations (Scopus)


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.

Original languageEnglish
Article number1561
JournalScientific reports
Publication statusPublished - 2013

Bibliographical note

Funding Information:
We would like to thank Dr. J. Chung, Dr. G. Thomas, and Dr. T. P. Neufeld for providing the fly stocks and Dr. H. H. Kim for providing the Flag-tagged TAK1 plasmid. We also thank Dr. Tamotsu Yoshimori for providing the GFP-LC3 plasmid and Se-Kyu Choi, Won-Ho Kim, and Dr. Oky Maeng for technological assistance. Especially, we thank Dr. Sujin Park, Dr. Kyung-Min Yang, Dr. Jin Muk Kang, and Staci Jakyong Kim for insightful discussions. Also, I thank Kyung Yun for helpful comments. Ook Joon Yoo was supported by the Research Program for Bio & Medical Technology Development through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2008-2004686). Heung Kyu Lee was supported by the NRF (2012028274) and the National R&D Program for Cancer Control (1020230). Seong-Jin Kim was supported by the NRF (2009-0081756) and MLTM (20046001).

All Science Journal Classification (ASJC) codes

  • General


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