DOI: 10.1073/pnas.251541198. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy

Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy

10.1073/pnas.251541198

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Muscle wasting is a debilitating consequence of fasting, inactivity, cancer, and other systemic diseases that results primarily from accelerated protein degradation by the ubiquitin-proteasome pathway. To identify key factors in this process, we have used cDNA microarrays to compare normal and atrophying muscles and found a unique gene fragment that is induced more than ninefold in muscles of fasted mice. We cloned this gene, which is expressed specifically in striated muscles. Because this mRNA also markedly increases in muscles atrophying because of diabetes, cancer, and renal failure, we named it atrogin-1. It contains a functional F-box domain that binds to Skp1 and thereby to Roc1 and Cul1, the other components of SCF-type Ub-protein ligases (E3s), as well as a nuclear localization sequence and PDZ-binding domain. On fasting, atrogin-1 mRNA levels increase specifically in skeletal muscle and before atrophy occurs. Atrogin-1 is one of the few examples of an F-box protein or Ub-protein ligase (E3) expressed in a tissue-specific manner and appears to be a critical component in the enhanced proteolysis leading to muscle atrophy in diverse diseases.

Bibliography

Gomes, M. D., Lecker, S. H., Jagoe, R. T., Navon, A., & Goldberg, A. L. (2001). Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proceedings of the National Academy of Sciences, 98(25), 14440â14445.

Authors 5

Marcelo D. Gomes (first)
Stewart H. Lecker (additional)
R. Thomas Jagoe (additional)
Ami Navon (additional)
Alfred L. Goldberg (additional)

References 42 Referenced 1,430

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J Sambrook, E F Fritsch, T Maniatis Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. Press, Plainview, NY, 1989). / Molecular Cloning: A Laboratory Manual by Sambrook J (1989)
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Dates

Type	When
Created	23 years ago (July 26, 2002, 10:35 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 9:47 a.m.)
Indexed	2 weeks, 1 day ago (Aug. 6, 2025, 8:16 a.m.)
Issued	23 years, 9 months ago (Nov. 20, 2001)
Published	23 years, 9 months ago (Nov. 20, 2001)
Published Online	23 years, 9 months ago (Nov. 20, 2001)
Published Print	23 years, 8 months ago (Dec. 4, 2001)

Funders 0

None

BibTeX

@article{Gomes_2001, title={Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.251541198}, DOI={10.1073/pnas.251541198}, number={25}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Gomes, Marcelo D. and Lecker, Stewart H. and Jagoe, R. Thomas and Navon, Ami and Goldberg, Alfred L.}, year={2001}, month=nov, pages={14440–14445} }

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