The Anti-inflammatory Prostaglandin 15-Deoxy-Δ12,14-PGJ2 Inhibits CRM1-dependent Nuclear Protein Export

被引：44

作者：

Hilliard, Mark ^{[2
]}

Frohnert, Cornelia ^{[1
]}

Spillner, Christiane ^{[1
]}

Marcone, Simone ^{[2
]}

Nath, Annegret ^{[1
]}

Lampe, Tina ^{[1
]}

Fitzgerald, Desmond J. ^{[2
]}

Kehlenbach, Ralph H. ^{[1
]}

机构：

[1] Univ Gottingen, Fac Med, Dept Biochem 1, D-37073 Gottingen, Germany

[2] UCD Conway Inst, Dublin 4, Ireland

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2010年 / 285卷 / 29期

关键词：

CYCLOPENTENONE PROSTAGLANDINS; PORE COMPLEX; LEPTOMYCIN-B; CRM1; J(2); IMPORT; BINDING; SIGNAL; TRANSPORT; RECEPTOR;

D O I：

10.1074/jbc.M110.131821

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The signaling molecule 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) has been described as the "anti-inflammatory prostaglandin." Here we show that substrates of the nuclear export receptor CRM1 accumulate in the nucleus in the presence of 15d-PGJ(2), identifying this prostaglandin as a regulator of CRM1-dependent nuclear protein export that can be produced endogenously. Like leptomycin B (LMB), an established fungal CRM1-inhibitor, 15d-PGJ(2) reacts with a conserved cysteine residue in the CRM1 sequence. This covalent modification prevents the formation of nuclear export complexes. Cells that are transfected with mutant CRM1(C528S) are resistant to the inhibitory effects of LMB and 15d-PGJ(2), demonstrating that the same single amino acid is targeted by the two compounds. Inhibition of the CRM1 pathway by endogenously produced prostaglandin and/or exogenously applied 15d-PGJ(2) may contribute to its anti-inflammatory, anti-proliferative, and anti-viral effects.

引用

页码：22202 / 22210

页数：9

共 53 条

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