You spin me round: MaFBx/Atrogin-1 feeds forward on FOXO transcription factors (like a record).
Poly-ubiquitin chains are post-translational modifications commonly used by the ubiquitin-proteasome system to mark proteins for degradation. The regulation of protein degradation plays an important role in regulating muscle cell size, a cellular process balanced by protein synthesis and catabolism. MaFBx/Atrogin-1, a muscle specific F-box protein, is a principle component of the SCF(atrogin-1) ubiquitin ligase complex that ubiquitinates and targets calcineurin for degradation, a key regulatory protein involved in pathologic hypertrophy. We have recently described a novel role for this ubiquitin ligase as a co-activator of the FOXO transcription factors through the catalysis of non-canonical poly-ubiquitin chain formation on FOXO proteins, an event that is sufficient to block Akt-dependent pathways involved in physiologic hypertrophy. In context with other reports describing the regulation and role of FOXO transcription factors, we present a working model for the role of atrogin-1 in both physiologic and pathologic hypertrophy.
Schisler
Jonathan C
JC
Carolina Cardiovascular Biology Center and Division of Cardiology, University of North Carolina, Chapel Hill, North Carolina 27599-7126, USA.
Willis
Monte S
MS
Patterson
Cam
C
D006332:Cardiomegaly / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D051858:Forkhead Transcription Factors; D009124:Muscle Proteins; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases