The Anaphase Promoting Complex/Cyclosome (APC/C): A Versatile E3 Ubiquitin Ligase

Curtis, Natalie L.; Bolaños-García, Víctor M.

doi:10.1007/978-3-030-28151-9_18

Cited by 7 publications

(3 citation statements)

References 393 publications

(424 reference statements)

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“…CDC20 plays a pivotal role in the regulation of chromosome segregation and mitotic exit. It exhibits dual, antagonistic functions in the SAC: it functions as an APC/C cofactor and activator (APC/C CDC20 ), but also as a core inhibitor of the APC/C in response to improper kinetochore-microtubule attachments ( Alfieri et al, 2016 ; Yamaguchi et al, 2016 ; Curtis and Bolanos-Garcia, 2019 ; Watson et al, 2019 ). For the latter role, CDC20 associates with BUBR1, MAD2 and BUB3, to form the Mitotic Checkpoint Complex, MCC, (CDC20 MCC ).…”

Section: Resultsmentioning

confidence: 99%

Biochemical, biophysical, and functional characterisation of the E3 ubiquitin ligase APC/C regulator CDC20 from Arabidopsis thaliana

et al. 2022

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The Anaphase Promoting Complex (APC/C), a large cullin-RING E3-type ubiquitin ligase, constitutes the ultimate target of the Spindle Assembly Checkpoint (SAC), an intricate regulatory circuit that ensures the high fidelity of chromosome segregation in eukaryotic organisms by delaying the onset of anaphase until each chromosome is properly bi-oriented on the mitotic spindle. Cell-division cycle protein 20 homologue (CDC20) is a key regulator of APC/C function in mitosis. The formation of the APC/CCDC20 complex is required for the ubiquitination and degradation of select substrates, which is necessary to maintain the mitotic state. In contrast to the roles of CDC20 in animal species, little is known about CDC20 roles in the regulation of chromosome segregation in plants. Here we address this gap in knowledge and report the expression in insect cells; the biochemical and biophysical characterisation of Arabidopsis thaliana (AtCDC20) WD40 domain; and the nuclear and cytoplasmic distribution of full-length AtCDC20 when transiently expressed in tobacco plants. We also show that most AtCDC20 degrons share a high sequence similarity to other eukaryotes, arguing in favour of conserved degron functions in AtCDC20. However, important exceptions were noted such as the lack of a canonical MAD1 binding motif; a fully conserved RRY-box in all six AtCDC20 isoforms instead of a CRY-box motif, and low conservation of key residues known to be phosphorylated by BUB1 and PLK1 in other species to ensure a robust SAC response. Taken together, our studies provide insights into AtCDC20 structure and function and the evolution of SAC signalling in plants.

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Section: Resultsmentioning

confidence: 99%

Biochemical, biophysical, and functional characterisation of the E3 ubiquitin ligase APC/C regulator CDC20 from Arabidopsis thaliana

et al. 2022

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“…This process is driven by increasing cyclin-dependent kinase (CDK) activity that needs to be reversed to allow mitotic exit. CDK activity is regulated by the Anaphase Promoting Complex (APC), an E3 ubiquitin ligase that targets cyclins for degradation and activates phosphatases such as Cdc14 to reverse CDK phosphorylation ( Peters, 2006 ; Curtis and Bolanos-Garcia, 2019 ; Lara-Gonzalez et al, 2021 ). While the roles of kinase and opposing phosphatase activities in mitotic progression are well understood, the contribution of other regulatory mechanisms such as translational control is less well studied.…”

Section: Introductionmentioning

confidence: 99%

Microtubule integrity regulates budding yeast RAM pathway gene expression

Lee

Biggins

2022

Front. Cell Dev. Biol.

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During mitosis, cells must spatiotemporally regulate gene expression programs to ensure accurate cellular division. Failures to properly regulate mitotic progression result in aneuploidy, a hallmark of cancer. Entry and exit from mitosis is largely controlled by waves of cyclin-dependent kinase (CDK) activity coupled to targeted protein degradation. The correct timing of CDK-based mitotic regulation is coordinated with the structure and function of microtubules. To determine whether mitotic gene expression is also regulated by the integrity of microtubules, we performed ribosome profiling and mRNA-sequencing in the presence and absence of microtubules in the budding yeast Saccharomyces cerevisiae. We discovered a coordinated translational and transcriptional repression of genes involved in cell wall biology processes when microtubules are disrupted. The genes targeted for repression in the absence of microtubules are enriched for downstream targets of a feed-forward pathway that controls cytokinesis and septum degradation and is regulated by the Cbk1 kinase, the Regulation of Ace2 Morphogenesis (RAM) pathway. We demonstrate that microtubule disruption leads to aberrant subcellular localization of Cbk1 in a manner that partially depends on the spindle position checkpoint. Furthermore, constitutive activation of the RAM pathway in the absence of microtubules leads to growth defects. Taken together, these results uncover a previously unknown link between microtubule function and the proper execution of mitotic gene expression programs to ensure that cell division does not occur prematurely.

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“…We then identified how DNA-PKcs regulates the ubiquitination and degradation of SIK2. The ubiquitin ligase APC/Cdc20 complex is involved in split sister chromosome segregation and spindle depolymerization, 5 which may be related to DNA-PKcs-mediated degradation and ubiquitination of SIK2. The Co-IP assay results revealed that DNA-PKcs and SIK2 interact with Cdc20 ( Fig.…”

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confidence: 99%

Ubiquitination and degradation of SIK2 by DNA-PKcs deficiency promote radiation-induced mitotic catastrophe

Zhu¹,

Zhang

Yan³

et al. 2023

Genes & Diseases

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The Anaphase Promoting Complex/Cyclosome (APC/C): A Versatile E3 Ubiquitin Ligase

Cited by 7 publications

References 393 publications

Biochemical, biophysical, and functional characterisation of the E3 ubiquitin ligase APC/C regulator CDC20 from Arabidopsis thaliana

Biochemical, biophysical, and functional characterisation of the E3 ubiquitin ligase APC/C regulator CDC20 from Arabidopsis thaliana

Microtubule integrity regulates budding yeast RAM pathway gene expression

Ubiquitination and degradation of SIK2 by DNA-PKcs deficiency promote radiation-induced mitotic catastrophe

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