Skeletal muscle atrophy is induced by Fbxw7β via atrogene upregulation

Kyungshin Shin, Young Gyu Ko, Jaemin Jeong, Heechung Kwon

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Muscle atrophy decreases skeletal muscle mass and is induced by inherited cachectic symptoms, genetic disorders, and sarcopenia. However, the molecular pathways associated with the onset of muscle atrophy are still unclear. In this study, we evaluated Fbxw7β, a gene associated with the development of muscle atrophy in vitro and in vivo. Among the three Fbxw7 isoforms, ectopically overexpressed Fbxw7β induced the expression of myogenin and major atrogene markers (atrogin-1 and MuRF-1) and reduced myoblast differentiation. In addition, endogenous expression of Fbxw7β was also upregulated by dexamethasone, which mimics muscle atrophy in vitro, accompanied by induction of myogenin and atrogene expression in primary myoblasts. Functional analysis of Fbxw7β using short hairpin RNA (shRNA) and a dominant-negative mutant (ΔFbox) suggested that Fbxw7β regulated muscle atrophy in vitro and in vivo. In particular, ΔFbox did not reduce the sizes of muscle fibers and did not induce myogenin and atrogene expression in vivo. Therefore, our findings demonstrated, for the first time, that Fbxw7β induced muscle atrophic phenotypes via atrogenes in adult muscle precursor cells and myofibers; this mechanism could be a potential therapeutic target for skeletal muscle atrophy.

Original languageEnglish
Pages (from-to)213-220
Number of pages8
JournalCell Biology International
Issue number2
Publication statusPublished - 2017 Feb 1

Bibliographical note

Funding Information:
This work was supported by the National R&D Program through the Korea Institute of Radiological and Medical Sciences funded by the Ministry of Science, ICT & Future Planning (grant nos. 1711031812 and 1711042677 to HK) in South Korea and from the Basic Science Research Program (grant no. 2014R1A1A1002599 to JJ) through the National Research Foundation of Korea funded by Medical Sciences funded by the Ministry of Science, ICT & Future Planning.

Publisher Copyright:
© 2016 International Federation for Cell Biology


  • Fbxw7β
  • atrogenes
  • dexamethasone
  • myogenin
  • skeletal muscle atrophy

ASJC Scopus subject areas

  • Cell Biology


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