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FBXL21 regulates diurnal proteostasis in skeletal muscle by targeting DNAJB6 and client proteins.
EMBO Reports · · Journal Article · Open access
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Abstract ↗AI summary
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FBXL21 regulates diurnal proteostasis in skeletal muscle by mediating degradation of DNAJB6 and its client proteins, including Desmin and TDP-43.
- Why it matters: Understanding circadian control of proteostasis is crucial for muscle health and may reveal therapeutic targets for myopathies, as this regulation remains poorly understood.
- What they did: The study identified DNAJB6 as a substrate of FBXL21, showing that FBXL21 promotes ubiquitination and proteasomal degradation of DNAJB6 and its clients in muscle cells, with effects observed in mutant mice and cell models.
- The result: Disruption of FBXL21 leads to abnormal accumulation of stress-related proteins, which can be rescued by muscle-specific FBXL21 expression, suggesting its potential as a therapeutic target for myopathies.
The findingWhy it mattersWhat they didThe result
- Open access