DOI: 10.1126/science.1079293. Endoproteolytic Activity of the Proteasome

Endoproteolytic Activity of the Proteasome

10.1126/science.1079293

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The proteasome plays a central role in the degradation of regulatory and misfolded proteins. Current models suggest that substrates access the internal catalytic sites by processively threading their termini through the gated substrate channel. Here, we found that latent (closed) and activated (open) proteasomes degraded two natively disordered substrates at internal peptide bonds even when they lacked accessible termini, suggesting that these substrates themselves promoted gating of the proteasome. This endoproteolysis provides a molecular mechanism for regulated release of transcription factors from inactive precursors as well as a means of accessing internal folding defects of misfolded multidomain proteins.

Bibliography

Liu, C.-W., Corboy, M. J., DeMartino, G. N., & Thomas, P. J. (2003). Endoproteolytic Activity of the Proteasome. Science, 299(5605), 408â411.

Authors 4

Chang-Wei Liu (first)
Michael J. Corboy (additional)
George N. DeMartino (additional)
Philip J. Thomas (additional)

References 34 Referenced 355

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The far-ultraviolet circular dichroism spectrum of the mixed population of circular and linear α-syns exhibits a predominant negative absorption at circa 198 nm characterisitic of a random coil conformation.
GFP fluorescence was stable during the degradation of the linear and circular GFP-p21 substrates as in Figs. 1 to 3.
10.1038/80992
10.1074/jbc.M204750200
10.1038/nsb0395-199
10.1074/jbc.274.32.22123
We thank S. J. Elledge (Baylor College of Medicine) for his generous gift of p21cDNA; R. Nussbaum(National Human Genome Research Institute) for α-syn cDNA; C. Wigley R. Stidham and S. Muallem for critical suggestions; and members of our laboratories for helpful comments. This work was supported by grants from the Welch Foundation (P.J.T.) Muscular Dystrophy Association (G.N.D.) and NIH [grants DK46818 (G.N.D.) and DK49835 (P.J.T.)].

Dates

Type	When
Created	22 years, 7 months ago (Jan. 16, 2003, 5:12 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 11:15 p.m.)
Indexed	3 weeks, 6 days ago (July 26, 2025, 5:22 a.m.)
Issued	22 years, 7 months ago (Jan. 17, 2003)
Published	22 years, 7 months ago (Jan. 17, 2003)
Published Print	22 years, 7 months ago (Jan. 17, 2003)

Funders 0

None

BibTeX

@article{Liu_2003, title={Endoproteolytic Activity of the Proteasome}, volume={299}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1079293}, DOI={10.1126/science.1079293}, number={5605}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Liu, Chang-Wei and Corboy, Michael J. and DeMartino, George N. and Thomas, Philip J.}, year={2003}, month=jan, pages={408–411} }

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