Osmotic stress inhibits proteasome by p38 MAPK-dependent phosphorylation

Seung Hoon Lee, Yoon Park, Sungjoo Kim Yoon, Jong Bok Yoon

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Osmotic stress causes profound perturbations of cell functions. Although the adaptive responses required for cell survival upon osmotic stress are being unraveled, little is known about the effects of osmotic stress on ubiquitin-dependent proteolysis. We now report that hyperosmotic stress inhibits proteasome activity by activating p38 MAPK. Osmotic stress increased the level of polyubiquitinated proteins in the cell. The selective p38 inhibitor SB202190 decreased osmotic stress-associated accumulation of polyubiquitinated proteins, indicating that p38 MAPK plays an inhibitory role in the ubiquitin proteasome system. Activated p38 MAPK stabilized various substrates of the proteasome and increased polyubiquitinated proteins. Proteasome preparations purified from cells expressing activated p38 MAPK had substantially lower peptidase activities than control proteasome samples. Proteasome phosphorylation sites dependent on p38 were identified by measuring changes in the extent of proteasome phosphorylation in response to p38 MAPK activation. The residue Thr-273 of Rpn2 is the major phosphorylation site affected by p38 MAPK. The mutation T273A in Rpn2 blocked the proteasome inhibition that is mediated by p38 MAPK. These results suggest that p38 MAPK negatively regulates the proteasome activity by phosphorylating Thr-273 of Rpn2.

Original languageEnglish
Pages (from-to)41280-41289
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number53
DOIs
Publication statusPublished - 2010 Dec 31

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Phosphorylation
Osmotic Pressure
p38 Mitogen-Activated Protein Kinases
Proteasome Endopeptidase Complex
Ubiquitin
Cells
Proteolysis
Proteins
Cell Survival
Peptide Hydrolases
Chemical activation
Mutation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, Seung Hoon ; Park, Yoon ; Yoon, Sungjoo Kim ; Yoon, Jong Bok. / Osmotic stress inhibits proteasome by p38 MAPK-dependent phosphorylation. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 53. pp. 41280-41289.
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Osmotic stress inhibits proteasome by p38 MAPK-dependent phosphorylation. / Lee, Seung Hoon; Park, Yoon; Yoon, Sungjoo Kim; Yoon, Jong Bok.

In: Journal of Biological Chemistry, Vol. 285, No. 53, 31.12.2010, p. 41280-41289.

Research output: Contribution to journalArticle

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