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Cell Cycle. 2008 Feb 15;7(4):440-3. Epub 2007 Dec 12.

You spin me round: MaFBx/Atrogin-1 feeds forward on FOXO transcription factors (like a record).

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1
Carolina Cardiovascular Biology Center and Division of Cardiology, University of North Carolina, Chapel Hill, North Carolina 27599-7126, USA.

Abstract

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.

PMID:
18235241
DOI:
10.4161/cc.7.4.5451
[Indexed for MEDLINE]
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