| Autor: |
Donaldson, Timothy D., Noureddine, Maher A., Reynolds, Patrick J., Bradford, William, Duronio, Robert J. |
| Zdroj: |
Molecular Biology of the Cell; November 2004, Vol. 15 Issue: 11 p4892-4903, 12p |
| Abstrakt: |
Cullin-dependent ubiquitin ligases regulate a variety of cellular and developmental processes by recruiting specific proteins for ubiquitin-mediated degradation. Cullin proteins form a scaffold for two functional modules: a catalytic module comprised of a small RING domain protein Roc1/Rbx1 and a ubiquitin-conjugating enzyme (E2), and a substrate recruitment module containing one or more proteins that bind to and bring the substrate in proximity to the catalytic module. Here, we present evidence that the three DrosophilaRoc proteins are not functionally equivalent. Mutation of Roc1acauses lethality that cannot be rescued by expression of Roc1bor Roc2by using the Roc1apromoter. Roc1amutant cells hyperaccumulate Cubitus interruptus, a transcription factor that mediates Hedgehog signaling. This phenotype is not rescued by expression of Roc2and only partially by expression of Roc1b. Targeted disruption of Roc1bcauses male sterility that is partially rescued by expression of Roc1aby using the Roc1bpromoter, but not by similar expression of Roc2. These data indicate that Roc proteins play nonredundant roles during development. Coimmunoprecipitation followed by Western or mass spectrometric analysis indicate that the three Roc proteins preferentially bind certain Cullins, providing a possible explanation for the distinct biological activities of each DrosophilaRoc/Rbx. |
| Databáze: |
Supplemental Index |
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