ASK1 negatively regulates the 26 S proteasome

Won Um Ji, Im Eunju, Park Joongkyu, Oh Yohan, Min Boram, Jung Lee Hyun, Bok Yoon Jong, Kwang Chul Chung

Research output: Contribution to journalArticle

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Abstract

The 26 S proteasome, composed of the 20 S core and 19 S regulatory particle, plays a central role in ubiquitin-dependent proteolysis. Disruption of this process contributes to the pathogenesis of the various diseases; however, the mechanisms underlying the regulation of 26 S proteasome activity remain elusive. Here, cell culture experiments and in vitro assays demonstrated that apoptosis signal-regulating kinase 1 (ASK1), a member of the MAPK kinase kinase family, negatively regulated 26 S proteasome activity. Immunoprecipitation/ Western blot analyses revealed that ASK1 did not interact with 20 S catalytic core but did interact with ATPases making up the 19 S particle, which is responsible for recognizing polyubiquitinated proteins, unfolding them, and translocating them into the 20 S catalytic core in an ATP-dependent process. Importantly, ASK1 phosphorylated Rpt5, an AAA ATPase of the 19 S proteasome, and inhibited its ATPase activity, an effect that may underlie the ability of ASK1 to inhibit 26 S proteasome activity. The current findings point to a novel role for ASK1 in the regulation of 26 S proteasome and offer new strategies for treating human diseases caused by proteasome malfunction.

Original languageEnglish
Pages (from-to)36434-36446
Number of pages13
JournalJournal of Biological Chemistry
Volume285
Issue number47
DOIs
Publication statusPublished - 2010 Nov 19

Fingerprint

MAP Kinase Kinase Kinase 5
Proteasome Endopeptidase Complex
Adenosine Triphosphatases
Catalytic Domain
Proteolysis
Protein Unfolding
Mitogen-Activated Protein Kinase Kinases
Ubiquitin
Cell culture
Immunoprecipitation
Assays
Phosphotransferases
Cell Culture Techniques
Adenosine Triphosphate
Western Blotting

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Ji, W. U., Eunju, I., Joongkyu, P., Yohan, O., Boram, M., Hyun, J. L., ... Chung, K. C. (2010). ASK1 negatively regulates the 26 S proteasome. Journal of Biological Chemistry, 285(47), 36434-36446. https://doi.org/10.1074/jbc.M110.133777
Ji, Won Um ; Eunju, Im ; Joongkyu, Park ; Yohan, Oh ; Boram, Min ; Hyun, Jung Lee ; Jong, Bok Yoon ; Chung, Kwang Chul. / ASK1 negatively regulates the 26 S proteasome. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 47. pp. 36434-36446.
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Ji, WU, Eunju, I, Joongkyu, P, Yohan, O, Boram, M, Hyun, JL, Jong, BY & Chung, KC 2010, 'ASK1 negatively regulates the 26 S proteasome', Journal of Biological Chemistry, vol. 285, no. 47, pp. 36434-36446. https://doi.org/10.1074/jbc.M110.133777

ASK1 negatively regulates the 26 S proteasome. / Ji, Won Um; Eunju, Im; Joongkyu, Park; Yohan, Oh; Boram, Min; Hyun, Jung Lee; Jong, Bok Yoon; Chung, Kwang Chul.

In: Journal of Biological Chemistry, Vol. 285, No. 47, 19.11.2010, p. 36434-36446.

Research output: Contribution to journalArticle

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Ji WU, Eunju I, Joongkyu P, Yohan O, Boram M, Hyun JL et al. ASK1 negatively regulates the 26 S proteasome. Journal of Biological Chemistry. 2010 Nov 19;285(47):36434-36446. https://doi.org/10.1074/jbc.M110.133777