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Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophyMuscle 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.
Document ID
20040088631
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Gomes, M. D.
(Harvard Medical School 240 Longwood Avenue, Boston, MA 02115, United States)
Lecker, S. H.
Jagoe, R. T.
Navon, A.
Goldberg, A. L.
Date Acquired
August 21, 2013
Publication Date
December 4, 2001
Publication Information
Publication: Proceedings of the National Academy of Sciences of the United States of America
Volume: 98
Issue: 25
ISSN: 0027-8424
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: DK02707
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Musculoskeletal
Non-NASA Center

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