| RRC ID |
77159
|
| 著者 |
Chiang S, Burch T, Van Domselaar G, Dick K, Radziwon A, Brusnyk C, Edwards MR, Piper J, Cutts T, Cao J, Li X, He R.
|
| タイトル |
The interaction between thymine DNA glycosylase and nuclear receptor coactivator 3 is required for the transcriptional activation of nuclear hormone receptors.
|
| ジャーナル |
Mol Cell Biochem
|
| Abstract |
The T:G mismatch specific DNA glycosylase (TDG) is known as an important enzyme in repairing damaged DNA. Recent studies also showed that TDG interacts with a p160 protein, steroid receptor coactivator 1 or nuclear receptor coactivator 1 (SRC1), and is involved in transcriptional activation of the estrogen receptor. However, whether other members of the p160 family are also involved in TDG-interaction and signal transduction regulation remains to be seen. In this study, we employed the mammalian two-hybrid system to investigate the interaction between TDG and another member of the p160 family, nuclear receptor coactivator 3 (NCoA-3). We found that a DXXD motif from aa 294-297 within TDG was responsible for the TDG-NCoA-3 interaction, we also found that a LLXXXL motif (X means any amino acid) from aa 1029-1037 (LLRNSL) and a merged LLXXL motif (LLDQLHTLL) from aa 1053-1061 in NCoA-3 were important for the TDG-NCoA-3 interactions. Mutation of the two aspartic acids (aa 294 and 297) into two alanines in TDG significantly affected the interaction and subsequent transcriptional activation of several steroid hormone receptors including, estrogen-, androgen- and progesterone- receptors in Huh7 cells. We also identified that mutations of NCoA-3 at either leucines 1029-1030 or 1053-1054 (replaced by alanines) also reduced the interaction activity between TDG and NCoA1. These data indicated that the TDG-NCoA-3 interaction is important for broad range activation of steroid hormone nuclear receptors, and may also contribute significantly to further understanding of TDG-related nuclear receptor regulation.
|
| 巻・号 |
333(1-2)
|
| ページ |
221-32
|
| 公開日 |
2010-1-1
|
| DOI |
10.1007/s11010-009-0223-1
|
| PMID |
19652917
|
| MeSH |
Amino Acid Motifs
Cell Line, Tumor
Humans
Mutagenesis, Site-Directed
Nuclear Receptor Coactivator 3 / metabolism*
Nuclear Receptor Coactivator 3 / physiology
Protein Interaction Mapping
Receptors, Cytoplasmic and Nuclear / genetics*
Thymine DNA Glycosylase / metabolism*
Thymine DNA Glycosylase / physiology
Transcriptional Activation*
Two-Hybrid System Techniques
|
| IF |
2.795
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-7 |
