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bioRxiv · 10.1101/2020.03.23.003210

Negative feedback between the APC/C and Cep152 at the centrosome regulates mitotic spindle assembly

Tischer, T.·Yang, J.·Barford, D.
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Abstract

The control of protein abundance is a fundamental regulatory mechanism during mitosis. The anaphase promoting complex/cyclosome (APC/C) is the main protein ubiquitin ligase responsible for the temporal regulation of mitotic progression. It has long been speculated that the APC/C might fulfil other functions including assembly of the mitotic spindle. Here, we show that the APC/C localizes to centrosomes, the organizers of the eukaryotic microtubule cytoskeleton, specifically during mitosis. The APC/C is recruited to spindle poles by the centrosomal protein Cep152, and we identified Cep152 as both a novel APC/C interaction partner, and as an APC/C substrate. Importantly, this revealed a mitotic function of Cep152 that is reciprocally regulated by the APC/C. A destruction-defective mutant of Cep152 showed that the timely regulation of Cep152 levels at the centrosome controls spindle assembly and chromosome segregation. The APC/C-mediated degradation of Cep152 at the centrosome releases Cep57 from an inhibitory complex to enable its interaction with pericentrin, a critical step in promoting microtubule nucleation. Thus, our study extends the function of the APC/C from being a regulator of mitosis to also acting as a positive governor of spindle assembly. The APC/C thereby integrates control of these two important processes in a temporal manner.

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Tischer, T., Yang, J., Barford, D.. 2020-03-23. Negative feedback between the APC/C and Cep152 at the centrosome regulates mitotic spindle assembly. https://doi.org/10.1101/2020.03.23.003210

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