| RRC ID |
54148
|
| 著者 |
Yuki R, Tatewaki T, Yamaguchi N, Aoyama K, Honda T, Kubota S, Morii M, Manabe I, Kuga T, Tomonaga T, Yamaguchi N.
|
| タイトル |
Desuppression of TGF-β signaling via nuclear c-Abl-mediated phosphorylation of TIF1γ/TRIM33 at Tyr-524, -610, and -1048.
|
| ジャーナル |
Oncogene
|
| Abstract |
Protein-tyrosine kinases regulate a broad range of intracellular processes occurring primarily just beneath the plasma membrane. With the greatest care to prevent dephosphorylation, we have shown that nuclear tyrosine phosphorylation regulates global chromatin structural states. However, the roles for tyrosine phosphorylation in the nucleus are poorly understood. Here we identify transcriptional intermediary factor 1-γ (TIF1γ/TRIM33/Ectodermin), which suppresses transforming growth factor-β (TGF-β) signaling through the association with Smad2/3 transcription factor, as a new nuclear substrate of c-Abl tyrosine kinase. Replacement of the three tyrosine residues Tyr-524, -610, and -1048 with phenylalanine (3YF) inhibits c-Abl-mediated phosphorylation of TIF1γ and enhances TIF1γ's association with Smad3. Importantly, knockdown-rescue experiments show that 3YF strengthens TIF1γ's ability to suppress TGF-β signaling. Intriguingly, activation of c-Abl by epidermal growth factor (EGF) induces desuppression of TGF-β signaling via enhancing the tyrosine phosphorylation level of TIF1γ. TGF-β together with EGF synergistically provokes desuppressive responses of epithelial-to-mesenchymal transition through tyrosine phosphorylation of TIF1γ. These results suggest that nuclear c-Abl-mediated tyrosine phosphorylation of TIF1γ has a desuppressive role in TGF-β-Smad2/3 signaling.
|
| 巻・号 |
38(5)
|
| ページ |
637-655
|
| 公開日 |
2019-1-1
|
| DOI |
10.1038/s41388-018-0481-z
|
| PII |
10.1038/s41388-018-0481-z
|
| PMID |
30177833
|
| MeSH |
A549 Cells
Animals
COS Cells
Chlorocebus aethiops
HeLa Cells
Humans
MCF-7 Cells
Phosphorylation
Proto-Oncogene Proteins c-abl / genetics
Proto-Oncogene Proteins c-abl / metabolism*
Signal Transduction*
Smad2 Protein / genetics
Smad2 Protein / metabolism
Smad3 Protein / genetics
Smad3 Protein / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism*
Transforming Growth Factor beta / genetics
Transforming Growth Factor beta / metabolism*
|
| IF |
7.971
|
| 引用数 |
4
|
| リソース情報 |
| 遺伝子材料 |
pCMFlag_hsSMAD3 (RDB07019)
pENTR4-H1 (RDB04395) |
