Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 384, Issue 1, Pages 219-227Publisher
ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2008.09.021
Keywords
proteasome inhibition; proline- and arginine-rich peptides; NF-kappa B; NMR
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Funding
- American Heart Association [0365134Y]
- NIH [5 R01 HL053793-11]
- American Heart Association Scientist Development [0635107N]
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PR39, a naturally occurring and cell-permeable proline- and arginine-rich peptide, blocks the degradation of inhibitor of nuclear factor kappa B (I kappa B alpha), thereby attenuating inflammation. It is a noncompetitive and reversible inhibitor of 20S proteasome. To identify its basis of action, we used solution NMR spectroscopy and mutational analyses of the active fragment, PR11, which identified amino acids required for human 20S proteasome inhibiting activity. We then examined PR11-mediated changes in the expression of nuclear factor kappa B-dependent genes in situ. The results provide prerequisites for proteasome inhibition by proline- and arginine-rich peptides, providing a powerful new tool to investigate inflammatory processes. These findings offer new leads in developing drugs to treat heart diseases or stroke. (c) 2008 Elsevier Ltd. All rights reserved.
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