| RRC ID |
65773
|
| 著者 |
Li Y, Sun X, Gao D, Ding Y, Liu J, Chen J, Luo J, Zhang J, Liu Q, Zhou Z.
|
| タイトル |
Dual functions of Rack1 in regulating Hedgehog pathway.
|
| ジャーナル |
Cell Death Differ
|
| Abstract |
Hedgehog (Hh) pathway plays multiple roles in many physiological processes and its dysregulation leads to congenital disorders and cancers. Hh regulates the cellular localization of Smoothened (Smo) and the stability of Cubitus interruptus (Ci) to fine-tune the signal outputs. However, the underlying mechanisms are still unclear. Here, we show that the scaffold protein Rack1 plays dual roles in Hh signaling. In the absence of Hh, Rack1 promotes Ci and Cos2 to form a Ci-Rack1-Cos2 complex, culminating in Slimb-mediated Ci proteolysis. In the presence of Hh, Rack1 dissociates from Ci-Rack1-Cos2 complex and forms a trimeric complex with Smo and Usp8, leading to Smo deubiquitination and cell surface accumulation. Furthermore, we find the regulation of Rack1 on Hh pathway is conserved from Drosophila to mammalian cells. Our findings demonstrate that Rack1 plays dual roles during Hh signal transduction and provide Rack1 as a potential drug target for Hh-related diseases.
|
| 巻・号 |
27(11)
|
| ページ |
3082-3096
|
| 公開日 |
2020-11-1
|
| DOI |
10.1038/s41418-020-0563-7
|
| PII |
10.1038/s41418-020-0563-7
|
| PMID |
32467643
|
| PMC |
PMC7560836
|
| MeSH |
Animals
Cell Line
Drosophila Proteins / genetics
Drosophila Proteins / metabolism*
Drosophila melanogaster / anatomy & histology
Drosophila melanogaster / embryology
Drosophila melanogaster / metabolism
Drosophila melanogaster / physiology
Hedgehog Proteins / genetics
Hedgehog Proteins / metabolism*
Receptors for Activated C Kinase / genetics
Receptors for Activated C Kinase / metabolism*
Signal Transduction / physiology*
Smoothened Receptor / genetics
Smoothened Receptor / metabolism*
Ubiquitin-Specific Proteases / genetics
Ubiquitin-Specific Proteases / metabolism*
|
| IF |
10.717
|
| リソース情報 |
| ショウジョウバエ |
6622R-1
GL00174
2055R-1
3412R-1
3412R-3 |
