論文 - 詳細
| RRC ID | 57748 |
|---|---|
| 著者 | Katoh I, Maehata Y, Moriishi K, Hata RI, Kurata SI. |
| タイトル | C-terminal α Domain of p63 Binds to p300 to Coactivate β-Catenin. |
| ジャーナル | Neoplasia |
| Abstract |
TP63 (p63), a member of the tumor suppressor TP53 (p53) gene family, is essential for ectodermal tissue development and suppresses malignant progression of carcinomas. The most abundant isoform, ΔNp63α (referred to as p63), lacks the N-terminal transactivation (TA) domain, and was originally characterized as a dominant-negative type suppressor against p53 family proteins. It also binds to TCF/LEF to inhibit β-catenin. Nevertheless, transcriptional activation by p63 has also been observed in varied systems. To understand the puzzling results, we analyzed the structure-function relationship of p63 in the control of β-catenin-dependent transcription. p63 acted as a suppressor of moderately induced β-catenin. However, when nuclear targeted S33Y β-catenin was applied to cause the maximum enhancer activation, p63 displayed a β-catenin-coactivating function. The DNA-binding domain of p63 and the target sequence facilitated it. Importantly, we newly found that, despite the absence of TA domain, p63 was associated with p300, a general adaptor protein and chromatin modifier causing transcriptional activation. C-terminal α domain of p63 was essential for p300-binding and for the coactivator function. These results were related to endogenous p63-p300 complex formation and Wnt/β-catenin-responsive gene regulation by p63 in squamous cell carcinoma lines. The novel p63-p300 interaction may be involved in positive regulation of gene expression in tissue development and carcinogenesis. |
| 巻・号 | 21(5) |
| ページ | 494-503 |
| 公開日 | 2019-5-1 |
| DOI | 10.1016/j.neo.2019.03.010 |
| PII | S1476-5586(19)30080-6 |
| PMID | 30986748 |
| PMC | PMC6462804 |
| MeSH | Bone Neoplasms / genetics Bone Neoplasms / metabolism Bone Neoplasms / pathology* E1A-Associated p300 Protein / genetics E1A-Associated p300 Protein / metabolism* Gene Expression Regulation, Neoplastic* Humans Osteosarcoma / genetics Osteosarcoma / metabolism Osteosarcoma / pathology* Protein Interaction Domains and Motifs Transcription Factors / genetics Transcription Factors / metabolism* Transcription, Genetic Transcriptional Activation Tumor Cells, Cultured Tumor Suppressor Protein p53 / metabolism Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism* beta Catenin / genetics beta Catenin / metabolism* |
| IF | 5.696 |
| 引用数 | 1 |
| 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 | Saos-2(RCB0428) |