FBXO25, an F-box protein homologue of atrogin-1, is not induced in atrophying muscle

• Published in: Biochimica et biophysica acta Vol. 1760; no. 6; pp. 966 - 972
• Main Authors: Maragno, Ana Leticia G.C., Baqui, Munira M.A., Gomes, Marcelo D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2006
• Subjects: Amino Acid Sequence; Animals; Atrogin-1; Atrophy; Cell Nucleus - metabolism; F-box; F-Box Proteins - chemistry; F-Box Proteins - genetics; F-Box Proteins - metabolism; FBXO25; Gene Expression Profiling; Gene Expression Regulation; Humans; Male; Mice; Molecular Sequence Data; Muscle Proteins - chemistry; Muscle Proteins - metabolism; Muscular Atrophy - metabolism; Proteasome; Protein Binding; Rats; Rats, Wistar; RNA, Messenger - genetics; RNA, Messenger - metabolism; S-Phase Kinase-Associated Proteins - metabolism; Sequence Alignment; SKP Cullin F-Box Protein Ligases - chemistry; SKP Cullin F-Box Protein Ligases - metabolism; Ubiquitin; Ubiquitin - metabolism; Ubiquitin-Protein Ligases - chemistry; Ubiquitin-Protein Ligases - metabolism; Atrophy; Ubiquitin; FBXO25; F-box; Atrogin-1; Proteasome
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2006.03.020

Atrogin-1/MAFbx/FBXO32 is a muscle-specific ubiquitin-ligase (E3) that is dramatically increased in atrophying muscle. Here, we have investigated the functional relationship between atrogin-1 and FBXO25 which shares 65% amino acid identity. Using a RT-PCR, we demonstrated that FBXO25 is highly expressed in brain, kidney, and intestine, whereas atrogin-1 expression is largely restricted to striate muscle. FBXO25 was shown here to contain a functional F-box domain that binds to Skp1 and thereby to Roc1 and Cul1, the major components of SCF-type E3s. In addition, the productive SCF complex containing FBXO25 showed ubiquitin ligase activity. We investigated the differential expression of atrogin-1 and FBXO25 in fasted and dexamethasone-treated mice and also in rats with streptozotocin-induced diabetes. Although the atrogin-1 was strongly induced in muscle in all three models, no changes were observed in the expression of FBXO25. Therefore, here we have shown that FBXO25 is a novel F-box protein analogous to atrogin-1, which is not involved in muscle atrophy. Further functional studies should elucidate the exact role of FBXO25 in the ubiquitin-proteasome pathway.