BUB-1-bound PLK-1 directs CDC-20 kinetochore recruitment to ensure timely embryonic mitoses.

Autor:	Houston J; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA., Ohta M; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA., Gómez-Cavazos JS; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA., Deep A; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA., Corbett KD; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA., Oegema K; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA., Lara-Gonzalez P; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA., Kim T; Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; Department of Biology Education, Pusan National University, Busan 46241, Republic of Korea. Electronic address: taekim@pusan.ac.kr., Desai A; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: abdesai@ucsd.edu.
Jazyk:	angličtina
Zdroj:	Current biology : CB [Curr Biol] 2023 Jun 05; Vol. 33 (11), pp. 2291-2299.e10. Date of Electronic Publication: 2023 May 02.
DOI:	10.1016/j.cub.2023.04.021
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu