Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy
Open accessAbstract
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.
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Muscle atrophy requires activation of gene transcription programs that regulate expression of atrophy-related genes (atrogenes).
“Muscle atrophy requires the activation of gene transcription programs that regulate the expression of a subset of genes that are named atrophy-related genes or atrogenes [10–14].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [12]
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- Authors
- Gomes, M. D., Lecker, S. H., Jagoe, R. T., Navon, A., & Goldberg, A. L.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-11-20
- Volume
- 98
- Issue
- 25
- Pages
- 14440-14445
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC64700
- OpenAlex
- W2100688137
- Cited by
- 1,774
- References
- 44
- Citations by year
- 2026: 40 · 2025: 43 · 2024: 53 · 2023: 45 · 2022: 61 · 2021: 68 · 2020: 89 · 2019: 85 · 2018: 85 · 2017: 77 · 2016: 84 · 2015: 98 · 2014: 98 · 2013: 119 · 2012: 105
- FWCI
- 11.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Muscular Dystrophy Association
- National Space Biomedical Research Institute
- US-UK Fulbright Commission
- National Institutes of Health (5k08dk002707-03, DK02707)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK02707)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- atrogin-1, muscle atrophy, F-box protein, ubiquitin-proteasome system, E3 ubiquitin ligase, SCF ubiquitin ligase, Skp1, ROC1, CUL1, skeletal muscle, fasting, protein degradation, diabetes mellitus, cancer, renal failure, PDZ-binding domain, nuclear localization signal, gene expression
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, Fasting, Ligases, Male, Mice, Inbred C57BL, Molecular Sequence Data, Muscle Proteins, Muscular Atrophy, RNA, Messenger, Gene Expression, DNA, Complementary, Oligonucleotide Array Sequence Analysis, SKP Cullin F-Box Protein Ligases, Mice
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