Eukaryotic initiation factor 2α-independent pathway of stress granule induction by the natural product pateamine A

Yongjun Dang, Nancy Kedersha, Woon Kai Low, Daniel Romo, Myriam Gorospe, Randal Kaufman, Paul Anderson, Jun Liu

Research output: Contribution to journalArticle

Abstract

Stress granules are aggregates of small ribosomal subunits, mRNA, and numerous associated RNA-binding proteins that include several translation initiation factors. Stress granule assembly occurs in the cytoplasm of higher eukaryotic cells under a wide variety of stress conditions, including heat shock, UV irradiation, hypoxia, and exposure to arsenite. Thus far, a unifying principle of eukaryotic initiation factor 2α phosphorylation prior to stress granule formation has been observed from the majority of experimental evidence. Pateamine A, a natural product isolated from marine sponge, was recently reported to inhibit eukaryotic translation initiation and induce the formation of stress granules. In this report, the protein composition and fundamental progression of stress granule formation and disassembly induced by pateamine A was found to be similar to that for arsenite. However, pateamine A-induced stress granules were more stable and less prone to disassembly than those formed in the presence of arsenite. Most significantly, pateamine A induced stress granules independent of eukaryotic initiation factor 2α phosphorylation, suggesting an alternative mechanism of formation from that previously described for other cellular stresses. Taking into account the known inhibitory effect of pateamine A on eukaryotic translation initiation, a model is proposed to account for the induction of stress granules by pateamine A as well as other stress conditions through perturbation of any steps prior to the rejoining of the 60S ribosomal subunit during the entire translation initiation process.

Original languageEnglish (US)
Pages (from-to)32870-32878
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number43
DOIs
StatePublished - Oct 27 2006

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Eukaryotic Initiation Factor-2
Biological Products
Eukaryotic Large Ribosome Subunits
Phosphorylation
Small Ribosome Subunits
Peptide Initiation Factors
RNA-Binding Proteins
Porifera
Eukaryotic Cells
pateamine A
Shock
Cytoplasm
Hot Temperature
Messenger RNA

ASJC Scopus subject areas

  • Biochemistry

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Eukaryotic initiation factor 2α-independent pathway of stress granule induction by the natural product pateamine A. / Dang, Yongjun; Kedersha, Nancy; Low, Woon Kai; Romo, Daniel; Gorospe, Myriam; Kaufman, Randal; Anderson, Paul; Liu, Jun.

In: Journal of Biological Chemistry, Vol. 281, No. 43, 27.10.2006, p. 32870-32878.

Research output: Contribution to journalArticle

Dang, Yongjun ; Kedersha, Nancy ; Low, Woon Kai ; Romo, Daniel ; Gorospe, Myriam ; Kaufman, Randal ; Anderson, Paul ; Liu, Jun. / Eukaryotic initiation factor 2α-independent pathway of stress granule induction by the natural product pateamine A. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 43. pp. 32870-32878.
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