Cited by 1,774Muscle Physiology and DisordersUbiquitin and proteasome pathwaysMuscle metabolism and nutrition

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

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Gomes, Marcelo D., Lecker, Stewart H., Jagoe, R. Thomas, Navon, Ami, Goldberg, Alfred L.·2001·Proceedings of the National Academy of Sciences

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.

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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
Published
2001-11-20
Volume
98
Issue
25
Pages
14440-14445
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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