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BUB-1-bound PLK-1 directs CDC-20 kinetochore recruitment to ensure timely embryonic mitoses.
- Source :
-
Current Biology . Jun2023, Vol. 33 Issue 11, p2291-2291. 1p. - Publication Year :
- 2023
-
Abstract
- During mitosis, chromosomes assemble kinetochores to dynamically couple with spindle microtubules. 1,2 Kinetochores also function as signaling hubs directing mitotic progression by recruiting and controlling the fate of the anaphase promoting complex/cyclosome (APC/C) activator CDC-20. 3,4,5 Kinetochores either incorporate CDC-20 into checkpoint complexes that inhibit the APC/C or dephosphorylate CDC-20, which allows it to interact with and activate the APC/C. 4,6 The importance of these two CDC-20 fates likely depends on the biological context. In human somatic cells, the major mechanism controlling mitotic progression is the spindle checkpoint. By contrast, progression through mitosis during the cell cycles of early embryos is largely checkpoint independent. 7,8,9,10 Here, we first show that CDC-20 phosphoregulation controls mitotic duration in the C. elegans embryo and defines a checkpoint-independent temporal mitotic optimum for robust embryogenesis. CDC-20 phosphoregulation occurs at kinetochores and in the cytosol. At kinetochores, the flux of CDC-20 for local dephosphorylation requires an ABBA motif on BUB-1 that directly interfaces with the structured WD40 domain of CDC-20. 6,11,12,13 We next show that a conserved "STP" motif in BUB-1 that docks the mitotic kinase PLK-1 14 is necessary for CDC-20 kinetochore recruitment and timely mitotic progression. The kinase activity of PLK-1 is required for CDC-20 to localize to kinetochores and phosphorylates the CDC-20-binding ABBA motif of BUB-1 to promote BUB-1-CDC-20 interaction and mitotic progression. Thus, the BUB-1-bound pool of PLK-1 ensures timely mitosis during embryonic cell cycles by promoting CDC-20 recruitment to the vicinity of kinetochore-localized phosphatase activity. • An optimal mitotic duration is important for robust C. elegans embryogenesis • Activation of CDC-20 at kinetochores controls embryonic mitotic duration • Kinetochore recruitment of CDC-20 by BUB-1 requires BUB-1-bound PLK-1 • Phosphorylation of BUB-1 by PLK-1 enhances binding and recruitment of CDC-20 Houston et al. show that an optimal mitotic duration set independently of the spindle checkpoint by phosphoregulation of CDC-20 ensures robust C. elegans embryogenesis. They also show that CDC-20 flux through kinetochores, which is important for its activation, requires BUB-1-bound PLK-1, whose kinase activity enhances CDC-20 binding to BUB-1. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09609822
- Volume :
- 33
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Current Biology
- Publication Type :
- Academic Journal
- Accession number :
- 164048453
- Full Text :
- https://doi.org/10.1016/j.cub.2023.04.021