COP9 signalosome component CSN-5 stabilizes PUF proteins FBF-1 and FBF-2 in Caenorhabditis elegans germline stem and progenitor cells.
Abstract — Entities Highlighted
Gene/ProteinChemicalDiseasePhenotypeAnatomyDev. Stage
RNA-binding proteins FBF-1 and FBF-2 (FBFs) are required for germline stem cell maintenance and the sperm/oocyte switch in Caenorhabditis elegans, although the mechanisms controlling FBF protein levels remain unknown. We identified an interaction between both FBFs and CSN-5), a component of the constitutive photomorphogenesis 9 (COP9) signalosome best known for its role in regulating protein degradation. Here, we find that the Mpr1/Pad1 N-terminal metalloprotease domain of CSN-5 interacts with the Pumilio and FBF RNA-binding domain of FBFs and the interaction is conserved for human homologs CSN5 and PUM1. The interaction between FBF-2 and CSN-5 can be detected in vivo by proximity ligation. csn-5 mutation results in the destabilization of FBF proteins, which may explain previously observed decrease in the numbers of germline stem and progenitor cells, and disruption of oogenesis. The loss of csn-5 does not decrease the levels of a related PUF protein PUF-3, and csn-5(lf) phenotype is not enhanced by fbf-1/2 knockdown, suggesting that the effect is specific to FBFs. The effect of csn-5 on oogenesis is largely independent of the COP9 signalosome and is cell autonomous. Surprisingly, the regulation of FBF protein levels involves a combination of COP9-dependent and COP9-independent mechanisms differentially affecting FBF-1 and FBF-2. This work supports a previously unappreciated role for CSN-5 in the stabilization of germline stem cell regulatory proteins FBF-1 and FBF-2.
Relation Network
Specialists Used
deepseek: 19gene_gene: 9gene_expression: 4
All Extracted Relations (33)
| Entity 1 | Relation | Entity 2 | Confidence | Specialist | Direction |
|---|---|---|---|---|---|
| FBF-1 | expressed in | germline | 100% | gene_expression | supports |
| PUF-3 | regulation | fbf-1 | 100% | gene_gene | supports |
| csn-5 | regulation | PUF-3 | 100% | gene_gene | supports |
| CSN-5 | regulation | FBF-1 | 100% | gene_gene | supports |
| csn-5 | regulation | fbf-1 | 100% | gene_gene | supports |
| CSN-5 | regulation | csn-5 | 100% | gene_gene | supports |
| FBF | expressed in | cell | 100% | gene_expression | supports |
| FBF-1 | expressed in | oocyte | 100% | gene_expression | supports |
| FBF | regulation | FBF-1 | 100% | gene_gene | supports |
| CSN-5 | expressed in | cell | 99% | gene_expression | supports |
| FBF-1 | regulation | FBF | 98% | gene_gene | supports |
| FBF | regulation | FBF | 98% | gene_gene | supports |
| CSN5 | binding | PUM1 | 85% | deepseek | supports |
| CSN-5 | regulates | FBF-2 | 85% | deepseek | supports |
| CSN-5 | positively regulates | germline stem cell regulatory proteins | 85% | deepseek | supports |
| FBF-1 | positively regulates | germline stem cell maintenance | 85% | deepseek | supports |
| FBF-2 | positively regulates | germline stem cell maintenance | 85% | deepseek | supports |
| FBF-1 | positively regulates | sperm/oocyte switch | 85% | deepseek | supports |
| FBF-2 | positively regulates | sperm/oocyte switch | 85% | deepseek | supports |
| FBF-1 | binding | CSN-5 | 85% | deepseek | supports |
| FBF-2 | binding | CSN-5 | 85% | deepseek | supports |
| CSN-5 | associated with | COP9 signalosome | 85% | deepseek | supports |
| CSN-5 | regulates | protein degradation | 85% | deepseek | supports |
| CSN-5 | positively regulates | FBF-1 | 85% | deepseek | supports |
| CSN-5 | positively regulates | FBF-2 | 85% | deepseek | supports |
| csn-5 | positively regulates | germline stem and progenitor cells | 85% | deepseek | supports |
| csn-5 | positively regulates | oogenesis | 85% | deepseek | supports |
| CSN-5 | negatively regulates | PUF-3 | 85% | deepseek | refutes |
| fbf-1 | genetic interaction | csn-5 | 85% | deepseek | supports |
| fbf-2 | genetic interaction | csn-5 | 85% | deepseek | supports |
| CSN-5 | regulates | FBF-1 | 85% | deepseek | supports |
| csn-5 | regulation | csn-5 | 75% | gene_gene | supports |
| FBF-1 | regulates | germline | 54% | — | supports |