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bioRxiv · 10.1101/2025.10.14.682142

Distinct D-Box Motifs in SPD-2 Mediate APC/CFZR-1 -Dependent Degradation and Centrosomal Localization in Caenorhabditis elegans

Yim, R. N.·Rivera, P.·DiPanni, J.·Song, M. H.
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Abstract

Centrosome duplication must be tightly regulated to maintain genomic stability. In Caenorhabditis elegans, the APC/C and co-activator FZR-1 function as negative regulators of centrosome duplication by targeting specific substrates for proteolytic degradation. While C. elegans SAS-5 and ZYG-1 have been identified as substrates of APC/CFZR-1, the mechanism by which APC/CFZR-1-dependent degradation influences centrosome assembly remains unclear. Here, we identified SPD-2, the conserved homolog of human CEP192, as a substrate of APC/CFZR-1. We show that loss of APC/CFZR-1 increases both cellular and centrosomal SPD-2 levels, and that SPD-2 physically associates with FZR-1 in vivo. Functional analyses of canonical D-box motifs reveal that D-box1, D-box2, and D-box3 each contribute to SPD-2 degradation, each with different functional consequences. Mutation of D-box3 alone partially rescued zyg-1 mutant phenotypes by restoring centrosome duplication and embryonic viability through increased centrosomal SPD-2 and ZYG-1. In contrast, mutating D-box1 or D-box2 elevated cellular SPD-2 but did not rescue zyg-1, with the D-box1 mutation further reducing centrosomal SPD-2 and exacerbating duplication defects and lethality in zyg-1 mutants. Our results reveal a conserved mechanism for APC/CFZR-1-dependent degradation of SPD-2 and show that its degron motifs have dual functions in degradation and centrosomal localization, ensuring robust control of centrosome assembly during C. elegans embryogenesis.

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Yim, R. N., Rivera, P., DiPanni, J., Song, M. H.. 2025-10-15. Distinct D-Box Motifs in SPD-2 Mediate APC/CFZR-1 -Dependent Degradation and Centrosomal Localization in Caenorhabditis elegans. https://doi.org/10.1101/2025.10.14.682142

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