Cardiovascular Research Advance Access originally published online on October 29, 2008
Cardiovascular Research 2009 81(3):439-448; doi:10.1093/cvr/cvn289
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Build it up–Tear it down: protein quality control in the cardiac sarcomere
1 Carolina Cardiovascular Biology Center, University of North Carolina, 8200 Medical Biomolecular Research Bldg, 103 Mason Farm Road, Chapel Hill, NC 27599-7126, USA
2 Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA
3 Department of Medicine, University of North Carolina, Chapel Hill, NC, USA
4 Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA
5 Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC, USA
* Corresponding author. Tel: +1 919 843 6477; fax: +1 919 843 4585. E-mail address: cpatters{at}med.unc.edu
The assembly and maintenance of the cardiac sarcomere, which contains the basic contractile components of actin and myosin, are essential for cardiac function. While often described as a static structure, the sarcomere is actually dynamic and undergoes constant turnover, allowing it to adapt to physiological changes while still maintaining function. A host of new factors have been identified that play a role in the regulation of protein quality control in the sarcomere, including chaperones that mediate the assembly of sarcomere components and ubiquitin ligases that control their specific degradation. There is clear evidence of sarcomere disorganization in animal models lacking muscle-specific chaperone proteins, illustrating the importance of these molecules in sarcomere structure and function. Although ubiquitin ligases have been found within the sarcomere structure itself, the role of the ubiquitin proteasome system in cardiac sarcomere regulation, and the factors that control its activity, are only just now being elucidated. The number of ubiquitin ligases identified with specificity for sarcomere proteins, each with distinct target substrates, is growing, allowing for tight regulation of this system. In this review, we highlight the dynamic interplay between sarcomere-specific chaperones and ubiquitin-dependent degradation of sarcomere proteins that is necessary in order to maintain structure and function of the cardiac sarcomere.
KEYWORDS Chaperones; Ubiquitin; Proteasome; Ubiquitin ligase; Muscle ring finger; Atrogin-1; MAFbx; C-terminal of Hsp70 interacting protein; MDM2; GimC; TriC; 
B-crystallin; UPD-2; UNC-45; Protein quality control
Time for primary review: 36 days
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