論文 - 詳細
| RRC ID | 84183 |
|---|---|
| 著者 | Kniazeva M, Ruvkun G. |
| タイトル | Translation elongation defects activate the Caenorhabditis elegans ZIP-2 bZIP transcription factor-mediated toxin defense. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
The Caenorhabditis elegans bZIP transcription factor ZIP-2 is activated by toxins or mutations that inhibit translational elongation. The zip-2 DNA-binding protein is encoded in a downstream main open reading frame (mORF), but under normal translation elongation conditions only an upstream overlapping oORF -1 frameshifted from mORF is translated. Mutations or toxins that slow translational elongation, but not inhibitors of translational initiation or termination, activate ZIP-2. An mORF initiation codon mutation does not disrupt the normal zip-2 response to translational elongation defects, suggesting that zip-2 activation does not depend on this ATG. An mORF early termination mutant can be activated by strong translation elongation inhibition, suggesting that translation initiated upstream on oORF +1 frameshifts when elongation is inhibited to the mORF reading frame downstream of the stop codon to activate a fused oORF/mORF ZIP-2 transcription factor. The protein and DNA sequences of zip-2 oORF and mORF are conserved across the Caenorhabditis, suggesting selection for particular codons sensitive to translational elongation defects. Mutations that disrupt the oORF initiation codon constitutively activate zip-2, but not if the mORF initiation codon is also mutant, showing that zip-2 oORF competes with mORF for translational initiation. oORF initiation codon mutation-activated zip-2 slows C. elegans growth, and this slow growth is suppressed by a zip-2 null mutation. A zip-2 null mutant also strongly suppresses the growth arrest caused by translational elongation inhibitors. Thus, ZIP-2 is both a sensor of translational elongation attack, and a defense regulatory output via its activation of response genes. |
| 巻・号 | 122(6) |
| ページ | e2423578122 |
| 公開日 | 2025-2-11 |
| DOI | 10.1073/pnas.2423578122 |
| PMID | 39899724 |
| PMC | PMC11831180 |
| MeSH | Animals Basic-Leucine Zipper Transcription Factors* / genetics Basic-Leucine Zipper Transcription Factors* / metabolism Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Mutation Open Reading Frames / genetics Peptide Chain Elongation, Translational* / genetics Protein Biosynthesis Toxins, Biological* |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm4248 |