F-box only protein 32 (FBXO32) (FBXO32)

F-box only protein 32 (FBXO32), widely known as Atrogin-1 or Muscle atrophy F-box protein (MAFbx), is a tissue-specific E3 ubiquitin ligase primarily expressed in skeletal and cardiac muscle (UniProt, 2021; NIH, 2001). It serves as the substrate-recognition component of the SCF (Skp1-Cullin1-F-box protein) ubiquitin ligase complex, targeting key proteins like the transcription factor MyoD and the translation initiation factor eIF3f for degradation via the 26S proteasome (PubMed, 2012). Atrogin-1 is highly induced during various muscle-wasting conditions, including fasting, cancer cachexia, diabetes, and disuse atrophy, often driven by the activation of FoxO transcription factors (PubMed Central, 2011; Antibodies Incorporated, 2023). While it is a critical mediator of muscle atrophy, it is also essential for muscle homeostasis; its absence can lead to myopathic phenotypes and cardiomyopathy (JCI Insight, 2024). Although there are currently no FDA-approved direct inhibitors, the pathway is indirectly modulated by growth factors like IGF-1 and beta-2 adrenergic agonists, making it a prominent therapeutic target for sarcopenia and other wasting syndromes (Company of Biologists, 2013).

Other names

Atrogin-1Muscle atrophy F-box proteinMAFbxFBXO32FBX32ATROGIN1

Functions as the substrate recognition component of the SCF E3 ubiquitin ligase complex, mediating the polyubiquitination and subsequent 26S proteasomal degradation of specific muscle proteins.