| RRC ID |
69910
|
| 著者 |
Min KD, Asakura M, Shirai M, Yamazaki S, Ito S, Fu HY, Asanuma H, Asano Y, Minamino T, Takashima S, Kitakaze M.
|
| タイトル |
ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Cardiogenesis requires the orchestrated spatiotemporal tuning of BMP signalling upon the balance between induction and counter-acting suppression of the differentiation of the cardiac tissue. SMADs are key intracellular transducers and the selective degradation of SMADs by the ubiquitin-proteasome system is pivotal in the spatiotemporal tuning of BMP signalling. However, among three SMADs for BMP signalling, SMAD1/5/9, only the specific E3 ligase of SMAD9 remains poorly investigated. Here, we report for the first time that SMAD9, but not the other SMADs, is ubiquitylated by the E3 ligase ASB2 and targeted for proteasomal degradation. ASB2, as well as Smad9, is conserved among vertebrates. ASB2 expression was specific to the cardiac region from the very early stage of cardiac differentiation in embryogenesis of mouse. Knockdown of Asb2 in zebrafish resulted in a thinned ventricular wall and dilated ventricle, which were rescued by simultaneous knockdown of Smad9. Abundant Smad9 protein leads to dysregulated cardiac differentiation through a mechanism involving Tbx2, and the BMP signal conducted by Smad9 was downregulated under quantitative suppression of Smad9 by Asb2. Our findings demonstrate that ASB2 is the E3 ligase of SMAD9 and plays a pivotal role in cardiogenesis through regulating BMP signalling.
|
| 巻・号 |
11(1)
|
| ページ |
23056
|
| 公開日 |
2021-11-29
|
| DOI |
10.1038/s41598-021-02390-0
|
| PII |
10.1038/s41598-021-02390-0
|
| PMID |
34845242
|
| PMC |
PMC8630118
|
| MeSH |
Animals
Bone Morphogenetic Proteins / metabolism
Cell Differentiation
Gene Expression Profiling
Gene Expression Regulation, Developmental
HEK293 Cells
Heart* / embryology
Humans
Mice
Oligonucleotide Array Sequence Analysis
Proteasome Endopeptidase Complex / metabolism
Signal Transduction
Smad8 Protein* / biosynthesis
Smad8 Protein* / physiology
Suppressor of Cytokine Signaling Proteins* / biosynthesis
Suppressor of Cytokine Signaling Proteins* / physiology
Ubiquitin / chemistry
Ubiquitin / physiology
Ubiquitin-Protein Ligases / metabolism
Zebrafish
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
P19.CL6(RCB2318) |
