論文 - 詳細
| RRC ID | 52103 |
|---|---|
| 著者 | Liu Z, Yanagisawa K, Griesing S, Iwai M, Kano K, Hotta N, Kajino T, Suzuki M, Takahashi T. |
| タイトル | TTF-1/NKX2-1 binds to DDB1 and confers replication stress resistance to lung adenocarcinomas. |
| ジャーナル | Oncogene |
| Abstract |
TTF-1, also known as NKX2-1, is a transcription factor that has indispensable roles in both lung development and physiology. We and others have reported that TTF-1 frequently exhibits high expression with increased copy number in lung adenocarcinomas, and also has a role as a lineage-survival oncogene through transcriptional activation of crucial target genes including ROR1 and LMO3. In the present study, we employed a global proteomic search for proteins that interact with TTF-1 in order to provide a more comprehensive picture of this still enigmatic lineage-survival oncogene. Our results unexpectedly revealed a function independent of its transcriptional activity, as TTF-1 was found to interact with DDB1 and block its binding to CHK1, which in turn attenuated ubiquitylation and subsequent degradation of CHK1. Furthermore, TTF-1 overexpression conferred resistance to cellular conditions under DNA replication stress (RS) and prevented an increase in consequential DNA double-strand breaks, as reflected by attenuated induction of pCHK2 and γH2AX. Our findings suggest that the novel non-transcriptional function of TTF-1 identified in this study may contribute to lung adenocarcinoma development by conferring tolerance to DNA RS, which is known to be inherently elicited by activation of various oncogenes. |
| 巻・号 | 36(26) |
| ページ | 3740-3748 |
| 公開日 | 2017-6-29 |
| DOI | 10.1038/onc.2016.524 |
| PII | onc2016524 |
| PMID | 28192407 |
| MeSH | Adenocarcinoma / genetics* Adenocarcinoma / metabolism* Adenocarcinoma / pathology Adenocarcinoma of Lung Cell Line, Tumor Checkpoint Kinase 1 / genetics Checkpoint Kinase 1 / metabolism DNA Breaks, Double-Stranded DNA Replication / physiology* DNA, Neoplasm / biosynthesis DNA, Neoplasm / genetics DNA-Binding Proteins / genetics* DNA-Binding Proteins / metabolism* Humans Lung Neoplasms / genetics* Lung Neoplasms / metabolism* Lung Neoplasms / pathology Transcription Factors Transcription, Genetic Ubiquitination |
| IF | 7.971 |
| 引用数 | 10 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | |
| 各媒体での言及数の合計 | 3 |
| 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 | PC-9(RCB4455) |