論文 - 詳細
| RRC ID | 73271 |
|---|---|
| 著者 | Ohe S, Kubota Y, Yamaguchi K, Takagi Y, Nashimoto J, Kozuka-Hata H, Oyama M, Furukawa Y, Takekawa M. |
| タイトル | ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II. |
| ジャーナル | Nat Commun |
| Abstract |
Growth factor-induced, ERK-mediated induction of immediate-early genes (IEGs) is crucial for cell growth and tumorigenesis. Although IEG expression is mainly regulated at the level of transcription elongation by RNA polymerase-II (Pol-II) promoter-proximal pausing and its release, the role of ERK in this process remains unknown. Here, we identified negative elongation factor (NELF)-A as an ERK substrate. Upon growth factor stimulation, ERK phosphorylates NELF-A, which dissociates NELF from paused Pol-II at the promoter-proximal regions of IEGs, allowing Pol-II to resume elongation and produce full-length transcripts. Furthermore, we found that in cancer cells, PP2A efficiently dephosphorylates NELF-A, thereby preventing aberrant IEG expression induced by ERK-activating oncogenes. However, when PP2A inhibitor proteins are overexpressed, as is frequently observed in cancers, decreased PP2A activity combined with oncogene-mediated ERK activation conspire to induce NELF-A phosphorylation and IEG upregulation, resulting in tumor progression. Our data delineate previously unexplored roles of ERK and PP2A inhibitor proteins in carcinogenesis. |
| 巻・号 | 13(1) |
| ページ | 7476 |
| 公開日 | 2022-12-3 |
| DOI | 10.1038/s41467-022-35230-4 |
| PII | 10.1038/s41467-022-35230-4 |
| PMID | 36463234 |
| PMC | PMC9719515 |
| MeSH | Carcinogenesis Genes, Immediate-Early* Humans Phosphorylation RNA Polymerase II* / genetics Transcription Factors |
| IF | 12.121 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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 | |
| ヒト・動物細胞 | 293(RCB1637) COS-7(RCB0539) HeLa(RCB0007) A549(RCB3677) A431(RCB0202) 293gp(RCB2354) |