Inhibition of Nonsense-mediated mRNA Decay by the Natural Product Pateamine A through Eukaryotic Initiation Factor 4AIII

被引：58

作者：

Dang, Yongjun ^{[1
]}

Low, Woon-Kai ^{[1
]}

Xu, Jing ^{[1
]}

Gehring, Niels H. ^{[5
,6
,7
]}

Dietz, Harry C. ^{[3
,4
]}

Romo, Daniel ^{[8
]}

Liu, Jun O. ^{[1
,2
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA

[5] Univ Heidelberg, Mol Med Partnership Unit, D-69120 Heidelberg, Germany

[6] European Mol Biol Lab, D-69120 Heidelberg, Germany

[7] Univ Heidelberg, Dept Pediat Oncol Hematol & Immunol, D-69120 Heidelberg, Germany

[8] Texas A&M Univ, Dept Chem, College Stn, TX 77842 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 35期

基金：

美国国家卫生研究院;

关键词：

EXON-JUNCTION COMPLEX; ZEALAND MARINE SPONGE; TRANSLATION INITIATION; CAENORHABDITIS-ELEGANS; UPF1; PHOSPHORYLATION; MAMMALIAN-CELLS; QUALITY-CONTROL; PROTEIN-KINASE; CORE COMPLEX; HUMAN SMG-1;

D O I：

10.1074/jbc.M109.009985

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：

Nonsense-mediated mRNA decay (NMD) in mammalian cells is a key mechanism for the removal of mRNA containing premature stop codons and is mediated by the coordinated function of numerous proteins that dynamically associate with the exon junction complex. The information communicated by these interactions and the functional consequences from a mechanistic perspective, however, are not completely documented. Herein, we report that the natural product pateamine A ( PatA) is capable of inhibiting NMD through direct interaction with eIF4AIII, which is independent of its inhibition of translation initiation. Furthermore, we have characterized the mechanisms by which PatA and cycloheximide modulate NMD. Unlike CHX, PatA was found to inhibit NMD by a novel mechanism that is independent of the phosphorylation of Up-frameshift protein 1.

引用

页码：23613 / 23621

页数：9

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