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Positive regulation of apoptosis signal-regulating kinase 1 by dual-specificity phosphatase 13A

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Abstract

Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase kinase kinase, is activated by several death stimuli and is tightly regulated by several mechanisms such as interactions with regulatory proteins and post-translational modifications. Here, we report that dual-specificity phosphatase 13A (DUSP13A) functions as a novel regulator of ASK1. DUSP13A interacts with the N-terminal domain of ASK1 and induces ASK1-mediated apoptosis through the activation of caspase-3. DUSP13A enhances ASK1 kinase activity and thus its downstream factors. Small interfering RNA (siRNA) analyses show that knock-down of DUSP13A in human neuroblastoma SK-N-SH cells reduces ASK1 kinase activity. The phosphatase activity of DUSP13A is not required for the regulation of ASK1. This regulatory action of DSUP13 on ASK1 activity involves competition with Akt1, a negative regulator of ASK1, for binding to ASK1. Taken together, this study provides novel insights into the role of DUSP13A in the precise regulation of ASK1.

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Acknowledgments

This work was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A01-0385-A70604-07M7-00040B) and by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (No. 2009-0072827).

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Authors and Affiliations

  1. Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea

    Jae Eun Park, Byoung Chul Park, Hyun-A Kim & Sung Goo Park

  2. College of Pharmacy, Chung-Ang University, Seoul, 156-756, Korea

    Mina Song, Hyung-Kyoon Choi & Sayeon Cho

  3. Department of Biotechnology, College of Natural Sciences, Seoul Women’s University, Seoul, 139-774, Korea

    Do Hee Lee

  4. Genome Research Center for Hematopoietic Diseases, Chonnam National University Hospital, Hwasun-gun, Jeonnam, 519-809, Korea

    Hyeoung-Joon Kim

  5. Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea

    Jong-Tae Kim

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  1. Jae Eun Park
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  2. Byoung Chul Park
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  3. Hyun-A Kim
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Correspondence to Sayeon Cho.

Additional information

J. E. Park and B. C. Park contributed equally to this work.

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Park, J.E., Park, B.C., Kim, HA. et al. Positive regulation of apoptosis signal-regulating kinase 1 by dual-specificity phosphatase 13A. Cell. Mol. Life Sci. 67, 2619–2629 (2010). https://doi.org/10.1007/s00018-010-0353-3

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  • DOI: https://doi.org/10.1007/s00018-010-0353-3

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