| RRC ID |
11712
|
| 著者 |
Nicholson SC, Nicolay BN, Frolov MV, Moberg KH.
|
| タイトル |
Notch-dependent expression of the archipelago ubiquitin ligase subunit in the Drosophila eye.
|
| ジャーナル |
Development
|
| Abstract |
archipelago (ago)/Fbw7 encodes a conserved protein that functions as the substrate-receptor component of a polyubiquitin ligase that suppresses tissue growth in flies and tumorigenesis in vertebrates. Ago/Fbw7 targets multiple proteins for degradation, including the G1-S regulator Cyclin E and the oncoprotein dMyc/c-Myc. Despite prominent roles in growth control, little is known about the signals that regulate Ago/Fbw7 abundance in developing tissues. Here we use the Drosophila eye as a model to identify developmental signals that regulate ago expression. We find that expression of ago mRNA and protein is induced by passage of the morphogenetic furrow (MF) and identify the hedgehog (hh) and Notch (N) pathways as elements of this inductive mechanism. Cells mutant for N pathway components, or hh-defective cells that express reduced levels of the Notch ligand Delta, fail to upregulate ago transcription in the region of the MF; reciprocally, ectopic N activation in eye discs induces expression of ago mRNA. A fragment of the ago promoter that contains consensus binding sites for the N pathway transcription factor Su(H) is bound by Su(H) and confers N-inducibility in cultured cells. The failure to upregulate ago in N pathway mutant cells correlates with accumulation of the SCF-Ago target Cyclin E in the area of the MF, and this is rescued by re-expression of ago. These data suggest a model in which N acts through ago to restrict levels of the pro-mitotic factor Cyclin E. This N-Ago-Cyclin E link represents a significant new cell cycle regulatory mechanism in the developing eye.
|
| 巻・号 |
138(2)
|
| ページ |
251-60
|
| 公開日 |
2011-1-1
|
| DOI |
10.1242/dev.054429
|
| PII |
dev.054429
|
| PMID |
21148181
|
| PMC |
PMC3005602
|
| MeSH |
Animals
Animals, Genetically Modified
Base Sequence
Cell Cycle
Cyclin E / metabolism
DNA Primers / genetics
Drosophila Proteins / chemistry
Drosophila Proteins / genetics*
Drosophila Proteins / metabolism
Drosophila melanogaster / genetics*
Drosophila melanogaster / growth & development*
Drosophila melanogaster / metabolism
Eye / cytology
Eye / growth & development*
Eye / metabolism*
F-Box Proteins / chemistry
F-Box Proteins / genetics*
F-Box Proteins / metabolism
Gene Expression Regulation, Developmental
Genes, Insect
Hedgehog Proteins / genetics
Mutation
Promoter Regions, Genetic
Protein Subunits
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Notch / genetics*
Receptors, Notch / metabolism
Signal Transduction
Ubiquitin-Protein Ligases / chemistry
Ubiquitin-Protein Ligases / genetics*
Ubiquitin-Protein Ligases / metabolism
|
| IF |
5.611
|
| 引用数 |
14
|
|
WOS 分野
|
DEVELOPMENTAL BIOLOGY
|
| リソース情報 |
| ショウジョウバエ |
P{GawB}ago[NP0850] (DGRC#103788) |
