A Key Role for the Ubiquitin Ligase UBR4 in Myofiber Hypertrophy in Drosophila and Mice
Open accessAbstract
Skeletal muscle cell (myofiber) atrophy is a detrimental component of aging and cancer that primarily results from muscle protein degradation via the proteasome and ubiquitin ligases. Transcriptional upregulation of some ubiquitin ligases contributes to myofiber atrophy, but little is known about the role that most other ubiquitin ligases play in this process. To address this question, we have used RNAi screening in Drosophila to identify the function of > 320 evolutionarily conserved ubiquitin ligases in myofiber size regulation in vivo. We find that whereas RNAi for some ubiquitin ligases induces myofiber atrophy, loss of others (including the N-end rule ubiquitin ligase UBR4) promotes hypertrophy. In Drosophila and mouse myofibers, loss of UBR4 induces hypertrophy via decreased ubiquitination and degradation of a core set of target proteins, including the HAT1/RBBP4/RBBP7 histone-binding complex. Together, this study defines the repertoire of ubiquitin ligases that regulate myofiber size and the role of UBR4 in myofiber hypertrophy.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
UBR4 is critical for hypertrophy and induces hypertrophy via ubiquitination and degradation of a core set of target proteins, including the HAT1/RBBP4/RBBP7 histone-binding complex, that control histone acetylation and expression of growth-promoting genes.
“However, a recent RNAi screening for the ubiquitin ligases that control muscle mass identified UBR4 as a critical one for hypertrophy37. UBR4 induces hypertrophy via ubiquitination and degradation of a core set of target proteins, including the HAT1/RBBP4/RBBP7 histone-binding complex, that control histone acetylation and expression of growth-promoting genes.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [37]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 61 · Cited by 90
- Authors
- Hunt, L. C., Stover, J., Haugen, B., Shaw, T. I., Li, Y., Pagala, V. R., Finkelstein, D., Barton, E. R., Fan, Y., Labelle, M., Peng, J., & Demontis, F.
- Affiliations
- St. Jude Children's Research Hospital (US)
- University of Florida (US)
- Corresponding author
- Demontis, Fabio
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 28
- Issue
- 5
- Pages
- 1268-1281.e6
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6697171
- OpenAlex
- W2965248489
- Cited by
- 90
- References
- 61
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 23 · 2023: 11 · 2022: 6 · 2021: 24 · 2020: 8
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Hartwell Foundation
- National Institute on Aging
- Ellison Medical Foundation
- American Parkinson Disease Association
- Glenn Foundation for Medical Research
- American Federation for Aging Research
- 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
- UBR4, ubiquitin ligase, muscle fiber hypertrophy, muscle fiber atrophy, skeletal muscle, muscle protein degradation, proteasome, N-end rule, ubiquitination, RNAi screen, Drosophila, mice
- MeSH terms
- Animals, Calmodulin-Binding Proteins, Drosophila melanogaster, Hypertrophy, Muscle Proteins, Myofibrils, Drosophila Proteins, Ubiquitin-Protein Ligases, Mice, Ubiquitination
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
