Molecular Basis for Proline- and Arginine-Rich Peptide Inhibition of Proteasome

被引：84

作者：

Anbanandam, Asokan ^{[1
]}

Albarado, Diana C. ^{[1
]}

Tirziu, Daniela C. ^{[2
,3
,4
]}

Simons, Michael ^{[2
,3
,4
]}

Veeraraghavan, Sudha ^{[1
]}

机构：

[1] Univ Texas Hlth Sci Ctr Houston, Dept Biochem & Mol Biol, Sch Med, Houston, TX 77030 USA

[2] Dartmouth Med Sch, Dartmouth Hitchcock Med Ctr, Angriogenesis Res Ctr, Dept Med, Lebanon, NH 03755 USA

[3] Dartmouth Med Sch, Dartmouth Hitchcock Med Ctr, Cardiol Sect, Lebanon, NH 03755 USA

[4] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT 06520 USA

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2008年 / 384卷 / 01期

关键词：

proteasome inhibition; proline- and arginine-rich peptides; NF-kappa B; NMR;

D O I：

10.1016/j.jmb.2008.09.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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.

引用

页码：219 / 227

页数：9

共 35 条

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Development of the proteasome inhihitor Veleade™ (Bortezomib) [J].