The Anti-inflammatory Prostaglandin 15-Deoxy-Δ12,14-PGJ2 Inhibits CRM1-dependent Nuclear Protein Export*
| Autor: | Desmond J. Fitzgerald, Simone Marcone, Tina Lampe, Annegret Nath, Christiane Spillner, Ralph H. Kehlenbach, Cornelia Frohnert, Mark Hilliard |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Cell Survival
Mutant Molecular Sequence Data Regulator Active Transport Cell Nucleus Anti-Inflammatory Agents Prostaglandin Receptors Cytoplasmic and Nuclear Biology Karyopherins Biochemistry environment and public health 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Humans Amino Acid Sequence Cysteine Nuclear protein Nuclear export signal Receptor Molecular Biology 030304 developmental biology Cell Nucleus 0303 health sciences Prostaglandin D2 fungi Transfection Cell Biology chemistry 030220 oncology & carcinogenesis Fatty Acids Unsaturated lipids (amino acids peptides and proteins) Mutant Proteins Peptides HeLa Cells |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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