Multiple Skp1-related proteins in Caenorhabditis elegans: diverse patterns of interaction with Cullins and F-box proteins.
BACKGROUND: The ubiquitin-proteasome pathway of proteolysis controls the abundance of specific regulatory proteins. The SCF complex is a type of ubiquitin-protein ligase (E3) that contributes to this pathway in many biological systems. In yeast and mammals, the SCF complex consists of common components, including Skp1, Cdc53/Cul1, and Rbx1, as well ... as variable components known as F-box proteins. Whereas only one functional Skp1 gene is present in the human genome, the genome of Caenorhabditis elegans has now been shown to contain at least 21 Skp1-related (skr) genes. The biochemical properties, expression, and function of the C. elegans SKR proteins were examined. RESULTS: Of the 17 SKR proteins examined, eight (SKR-1, -2, -3, -4, -7, -8, -9, and -10) were shown to interact with C. elegans CUL1 by yeast two-hybrid analysis or a coimmunoprecipitation assay in mammalian cells. Furthermore, SKR proteins exhibited diverse binding specificities for C. elegans F-box proteins. The tissue specificity of expression of the CUL1-interacting SKR proteins was also varied. Suppression of skr-1 or skr-2 genes by double-stranded RNA interference resulted in embryonic death, whereas that of skr-7, -8, -9, or -10 was associated with slow growth and morphological abnormalities. CONCLUSIONS: The multiple C. elegans SKR proteins exhibit marked differences in their association with Cullins and F-box proteins, in tissue specificity of expression, and in phenotypes associated with functional suppression by RNAi. At least eight of the SKR proteins may, like F-box proteins, act as variable components of the SCF complex in C. elegans.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Cycle Proteins, Cloning, Molecular, Cullin Proteins, Gene Expression Regulation, Humans, Molecular Sequence Data, Phylogeny, Protein Binding, RNA, Double-Stranded, RNA, Messenger, S-Phase Kinase-Associated Proteins, Sequence Homology, Amino Acid, Transfection, Two-Hybrid System Techniques
Amino Acid Motifs, Amino Acid Sequence, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Cycle Proteins, Cloning, Molecular, Cullin Proteins, Gene Expression Regulation, Humans, Molecular Sequence Data, Phylogeny, Protein Binding, RNA, Double-Stranded, RNA, Messenger, S-Phase Kinase-Associated Proteins, Sequence Homology, Amino Acid, Transfection, Two-Hybrid System Techniques
Curr. Biol.
Date: Feb. 19, 2002
PubMed ID: 11864566
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