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

Jack Houston; Midori Ohta; J Sebastián Gómez-Cavazos; Amar Deep; Kevin D Corbett; Karen Oegema; Pablo Lara-Gonzalez; Taekyung Kim; Arshad Desai

doi:10.1016/j.cub.2023.04.021

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

Curr Biol. 2023 Jun 5;33(11):2291-2299.e10. doi: 10.1016/j.cub.2023.04.021. Epub 2023 May 2.

Authors

Jack Houston¹, Midori Ohta², J Sebastián Gómez-Cavazos³, Amar Deep⁴, Kevin D Corbett⁵, Karen Oegema⁶, Pablo Lara-Gonzalez⁷, Taekyung Kim⁸, Arshad Desai⁹

Affiliations

¹ 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.
² 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.
³ 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.
⁴ Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
⁵ 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.
⁶ 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.
⁷ 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.
⁸ 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.
⁹ 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.

PMID: 37137308
PMCID: PMC10270731 (available on 2024-06-05)
DOI: 10.1016/j.cub.2023.04.021

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-1¹⁴ 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.

Keywords: APC/C; Bub1; Cdc20; Plk1; cell cycle; centromere; embryogenesis; kinetochore; mitosis; spindle assembly checkpoint.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Anaphase-Promoting Complex-Cyclosome / metabolism
Animals
Caenorhabditis elegans* / genetics
Cdc20 Proteins / metabolism
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Centers for Disease Control and Prevention, U.S.
Kinetochores* / metabolism
Mitosis
Spindle Apparatus / metabolism
United States

Substances

Anaphase-Promoting Complex-Cyclosome
Cdc20 Proteins
Cell Cycle Proteins
plk-1 protein, C elegans
FZY-1 protein, C elegans
bub-1 protein, C elegans

Abstract

Publication types

MeSH terms

Substances

Grants and funding