Cyclin B3 activates the Anaphase-Promoting Complex/Cyclosome in meiosis and mitosis

Abstract

In mitosis and meiosis, chromosome segregation is triggered by the Anaphase-Promoting Complex/Cyclosome (APC/C), a multi-subunit ubiquitin ligase that targets proteins for degradation, leading to the separation of chromatids. APC/C activation requires phosphorylation of its APC3 and APC1 subunits, which allows the APC/C to bind its Cdc20 co-activator. The identity of the kinase(s) responsible for APC/C activation in vivo is unclear. Cyclin B3 is required for meiotic anaphase in flies, worms and vertebrates, but whether it activates the APC/C is unclear. We found that Drosophila Cyclin B3 (CycB3) collaborates with PP2A-B55/Tws in embryonic development, indicating that CycB3 also promotes anaphase in mitosis. Moreover, CycB3 promotes APC/C activity and anaphase in cells in culture. We show that CycB3 physically associates with the APC/C, is required for phosphorylation of APC3, and promotes APC/C association with its co-activators. We propose that CycB3-Cdk1 directly phosphorylates the APC/C to activate it in both meiosis and mitosis.

Mitotic checkpoint regulator RAE1 promotes tumor growth in colorectal cancer

“…To investigate whether RAE1 could be a therapeutic target, we performed a comprehensive analysis of 276 genes encoding microtubule‐regulating proteins 19,23‐31 using TCGA data and evaluated their potential efficacy as a therapeutic target. We calculated the fold change in mRNA expression of each gene in tumor tissues compared to normal tissues, the correlation between mRNA expression and DNA copy number, and whether the high expression group was associated with poor prognosis.…”

Cyclin B3 implements timely vertebrate oocyte arrest for fertilization

“…In Drosophila, cyclin B3 was shown to promote anaphase onset during early embryonic mitotic divisions and female meiosis, but is dispensable later in development. Flies without zygotic cyclin B3 are viable but again, females and not males are infertile (Garrido et al, 2020;Jacobs et al, 1998;Yuan and O'Farrell, 2015). Notably, Drosophila lacks a true Emi2 orthologue and indeed it has been shown that Drosophila cyclin B3 directly activates the APC/C to promote anaphase in meiosis (Garrido et al, 2020).…”

Dynamic Alterations of the Distal Intestinal Microbiota, Transcriptome, and Metabolome of Hybrid Grouper by β -Conglycinin With Reconciliations by Sodium Butyrate in Feed

“…Mitosis plays an important role in maintaining normal growth and development of individuals (Sanz-Gómez et al, 2020). G2/mitotic-specific cyclin-B1 (Xie et al, 2019), B2 (Waesch andCross, 2002), and B3 (Garrido et al, 2020) are three proteins essential for mitosis, and their deletion or inhibition of expression usually results in varying degrees of cellular damage, consequently affecting cellular function. We observed that these three cyclins were significantly downregulated, and the expression of genes related to cell cycle regulatory proteins and chromosome structure maintenance, such as cyclin-F (D'Angiolella et al, 2012), double-strand break repair protein (Sinha et al, 2020), and structural maintenance of chromosome protein 2 (Heidelberg, 2011) were inhibited.…”