Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 7 December 2010
Vol. 3, Issue 151, p. ra88
[DOI: 10.1126/scisignal.2001232]


Regulation of the 26S Proteasome Complex During Oxidative Stress

Xiaorong Wang1,2, James Yen3*, Peter Kaiser3{dagger}, and Lan Huang1,2{dagger}

1 Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.
2 Department of Developmental and Cell Biology, University of California, Irvine, CA 92697, USA.
3 Department of Biological Chemistry, University of California, Irvine, CA 92697, USA.

* Present address: Zymo Research Corporation, Orange, CA 92867, USA.

Abstract: The proteasome plays a pivotal role in the cellular response to oxidative stress. Here, we used biochemical and mass spectrometric methods to investigate structural changes in the 26S proteasomes from yeast and mammalian cells exposed to hydrogen peroxide (H2O2). Oxidative stress induced the dissociation of the 20S core particle from the 19S regulatory particle of the 26S proteasome, which resulted in loss of the activities of the 26S proteasome and accumulation of ubiquitinated proteins. H2O2 triggered the increased association of the proteasome-interacting protein Ecm29 with the purified 19S particle. Deletion of ECM29 in yeast cells prevented the disassembly of the 26S proteasome in response to oxidative stress, and ecm29 mutants were more sensitive to H2O2 than were wild-type cells, suggesting that separation of the 19S and 20S particles is important for cellular recovery from oxidative stress. The increased amount of free 20S core particles was required to degrade oxidized proteins. The Ecm29-dependent dissociation of the proteasome was independent of Yap1, a transcription factor that is critical for the oxidative stress response in yeast, and thus functions as a parallel defense pathway against H2O2-induced stress.

{dagger} To whom correspondence should be addressed. E-mail: lanhuang{at} (L.H.); pkaiser{at} (P.K.)

Citation: X. Wang, J. Yen, P. Kaiser, L. Huang, Regulation of the 26S Proteasome Complex During Oxidative Stress. Sci. Signal. 3, ra88 (2010).

Read the Full Text

NADH Binds and Stabilizes the 26S Proteasomes Independent of ATP.
P. Tsvetkov, N. Myers, R. Eliav, Y. Adamovich, T. Hagai, J. Adler, A. Navon, and Y. Shaul (2014)
J. Biol. Chem. 289, 11272-11281
   Abstract »    Full Text »    PDF »
Regulation of Acetylation Restores Proteolytic Function of Diseased Myocardium in Mouse and Human.
D. Wang, C. Fang, N. C. Zong, D. A. Liem, M. Cadeiras, S. B. Scruggs, H. Yu, A. K. Kim, P. Yang, M. Deng, et al. (2013)
Mol. Cell. Proteomics 12, 3793-3802
   Abstract »    Full Text »    PDF »
The Proteasome-associated Protein Ecm29 Inhibits Proteasomal ATPase Activity and in Vivo Protein Degradation by the Proteasome.
A. De La Mota-Peynado, S. Y.-C. Lee, B. M. Pierce, P. Wani, C. R. Singh, and J. Roelofs (2013)
J. Biol. Chem. 288, 29467-29481
   Abstract »    Full Text »    PDF »
Subcellular Distribution and Dynamics of Active Proteasome Complexes Unraveled by a Workflow Combining in Vivo Complex Cross-Linking and Quantitative Proteomics.
B. Fabre, T. Lambour, J. Delobel, F. Amalric, B. Monsarrat, O. Burlet-Schiltz, and M.-P. Bousquet-Dubouch (2013)
Mol. Cell. Proteomics 12, 687-699
   Abstract »    Full Text »    PDF »
Proteomics Propels Protein Degradation Studies in San Diego.
E. J. Bennett and T. Mayor (2012)
Mol. Cell. Proteomics 11, 1523-1528
   Abstract »    Full Text »    PDF »
Mapping the Structural Topology of the Yeast 19S Proteasomal Regulatory Particle Using Chemical Cross-linking and Probabilistic Modeling.
A. Kao, A. Randall, Y. Yang, V. R. Patel, W. Kandur, S. Guan, S. D. Rychnovsky, P. Baldi, and L. Huang (2012)
Mol. Cell. Proteomics 11, 1566-1577
   Abstract »    Full Text »    PDF »
Structural Defects in the Regulatory Particle-Core Particle Interface of the Proteasome Induce a Novel Proteasome Stress Response.
S. Park, W. Kim, G. Tian, S. P. Gygi, and D. Finley (2011)
J. Biol. Chem. 286, 36652-36666
   Abstract »    Full Text »    PDF »
Loss of Rpt5 Protein Interactions with the Core Particle and Nas2 Protein Causes the Formation of Faulty Proteasomes That Are Inhibited by Ecm29 Protein.
S. Y.-C. Lee, A. De La Mota-Peynado, and J. Roelofs (2011)
J. Biol. Chem. 286, 36641-36651
   Abstract »    Full Text »    PDF »
Proteasome Activator 200: The HEAT is on....
A. F. Savulescu and M. H. Glickman (2011)
Mol. Cell. Proteomics 10, R110.006890
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 7 December 2010.
L. Huang and A. M. VanHook (2010)
Science Signaling 3, pc22
   Abstract »    Full Text »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882