| RRC ID |
42882
|
| 著者 |
Idogawa M, Masutani M, Shitashige M, Honda K, Tokino T, Shinomura Y, Imai K, Hirohashi S, Yamada T.
|
| タイトル |
Ku70 and poly(ADP-ribose) polymerase-1 competitively regulate beta-catenin and T-cell factor-4-mediated gene transactivation: possible linkage of DNA damage recognition and Wnt signaling.
|
| ジャーナル |
Cancer Res
|
| Abstract |
Formation of the T-cell factor-4 (TCF-4) and beta-catenin nuclear complex is considered crucial to embryonic development and colorectal carcinogenesis. We previously reported that poly(ADP-ribose) polymerase-1 (PARP-1) interacts with the TCF-4 and beta-catenin complex and enhances its transcriptional activity. However, its biological significance remains unexplained. Using immunoprecipitation and mass spectrometry, we found that two Ku proteins, Ku70 and Ku80, were also associated with the complex. Knockdown of Ku70 by RNA interference increased the amount of beta-catenin associated with TCF-4 and enhanced the transcriptional activity. PARP-1 competed with Ku70 for binding to TCF-4. Treatment with bleomycin, a DNA-damaging alkylating agent, induced polyADP-ribosylation of PARP-1 protein and inhibited its interaction with TCF-4. Bleomycin conversely increased the amounts of Ku70 coimmunoprecipitated with TCF-4 and removed beta-catenin from TCF-4. We propose a working model in which the transcriptional activity of TCF-4 is regulated by the relative amount of Ku70, PARP-1, and beta-catenin proteins binding to TCF-4. Identification of the functional interaction of Ku70 as well as PARP-1 with the TCF-4 and beta-catenin transcriptional complex may provide insights into a novel linkage between DNA damage recognition/repair and Wnt signaling.
|
| 巻・号 |
67(3)
|
| ページ |
911-8
|
| 公開日 |
2007-2-1
|
| DOI |
10.1158/0008-5472.CAN-06-2360
|
| PII |
67/3/911
|
| PMID |
17283121
|
| MeSH |
Animals
Antigens, Nuclear / genetics
Antigens, Nuclear / metabolism*
Cell Line
Cell Nucleus / genetics
Cell Nucleus / metabolism
DNA Damage / physiology*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
HCT116 Cells
Humans
Ku Autoantigen
Mice
Mice, Knockout
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases / metabolism*
Protein Binding
Protein Structure, Tertiary
Signal Transduction
TCF Transcription Factors / antagonists & inhibitors
TCF Transcription Factors / genetics
TCF Transcription Factors / metabolism*
Transcription Factor 7-Like 2 Protein
Transcriptional Activation
Transfection
Wnt Proteins / metabolism*
beta Catenin / antagonists & inhibitors
beta Catenin / genetics
beta Catenin / metabolism*
|
| IF |
9.727
|
| 引用数 |
55
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
