| RRC ID |
73801
|
| 著者 |
Liu S, Baeg GH, Yang Y, Goh FG, Bao H, Wagner EJ, Yang X, Cai Y.
|
| タイトル |
The Integrator complex desensitizes cellular response to TGF-β/BMP signaling.
|
| ジャーナル |
Cell Rep
|
| Abstract |
Maintenance of stem cells requires the concerted actions of niche-derived signals and stem cell-intrinsic factors. Although Decapentaplegic (Dpp), a Drosophila bone morphogenetic protein (BMP) molecule, can act as a long-range morphogen, its function is spatially limited to the germline stem cell niche in the germarium. We show here that Integrator, a complex known to be involved in RNA polymerase II (RNAPII)-mediated transcriptional regulation in the nucleus, promotes germline differentiation by restricting niche-derived Dpp/BMP activity in the cytoplasm. Further results show that Integrator works in various developmental contexts to desensitize the cellular response to Dpp/BMP signaling during Drosophila development. Mechanistically, our results show that Integrator forms a multi-subunit complex with the type I receptor Thickveins (Tkv) and other Dpp/BMP signaling components and acts in a negative feedback loop to promote Tkv turnover independent of its transcriptional activity. Similarly, human Integrator subunits bind transforming growth factor β (TGF-β)/BMP signaling components and antagonize their activity, suggesting a conserved role of Integrator across metazoans.
|
| 巻・号 |
42(1)
|
| ページ |
112007
|
| 公開日 |
2023-1-31
|
| DOI |
10.1016/j.celrep.2023.112007
|
| PII |
S2211-1247(23)00018-9
|
| PMID |
36641752
|
| MeSH |
Animals
Bone Morphogenetic Proteins / metabolism
Cell Differentiation / physiology
Drosophila / metabolism
Drosophila Proteins* / genetics
Drosophila Proteins* / metabolism
Humans
Protein Serine-Threonine Kinases / metabolism
Receptors, Cell Surface / metabolism
Signal Transduction / physiology
Transforming Growth Factor beta* / metabolism
|
| IF |
8.109
|
| リソース情報 |
| ショウジョウバエ |
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