CCNB:CDK1 phosphorylates BORA

Stable Identifier
R-HSA-4086410
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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CDK1 in complex with cyclin B was shown to phosphorylate both human and Drosophila BORA protein, with BORA showing remarkable evolutionary conservation (Hutterer et al. 2006). CCNB1:CDK1 complex was shown to phosphorylate human BORA on an evolutionarily conserved serine residue S252, which provides a docking site for PLK1 (Chan et al. 2008). By liquid chromatography-tandem mass spectrometry (LC-MS/MS) mapping of in vivo and in vitro (using CCNB1:CDK1 complex) CDK1-dependent phosphorylation sites in human BORA during G2 phase in human cells, nine evolutionarily conserved residues were identified, reported at least once in vivo and once in vitro: T15, S27, S41, T52, S112, S252, S274, S278, and S375 (Thomas et al. 2016). The N-terminal fragment of BORA, consisting of the first 225 amino acids, was found to be sufficient to support PLK1 activation, and, of the CDK1-dependent phospho sites, S41 and S112 were found to be particularly important (Thomas et al. 2016). BORA was not detected in the CCNA2 co-immunoprecipitate 4 hours after release of the double thymidine block, but was detected in the CCNB1 co-immunoprecipitate, although both CCNA2:CDK1 and CCNB1:CDK1 are active at the 4 h mark, implicating CCNB1:CDK1 as the main BORA kinase (Thomas et al. 2016). However, BORA was recovered from the cytosolic CCNA2 co-immunoprecipitate at the start of G2 (Silva Cascales et al. 2021) and was shown to be phosphorylated in vitro by CCNA2:CDK2 complex (Silva Cascales et al. 2021, Tavernier et al. 2021). As CDK1 is critical for in vivo cytosolic localization of CCNA2 at the start of G2 phase, and as cytosolic localization of CCNA2 is critical for BORA-mediated PLK1 activation, it is plausible that CCNA:CDK1 complexes perform the initial phosphorylation of BORA, and that CCNB:CDK1 becomes the predominant BORA kinase later in G2 (Silva Cascales et al. 2021). In Xenopus egg extracts, Ccna:Cdk1 mediates phosphorylation of Bora on a conserved residue S110 (corresponds to S112 in human BORA), which promotes Aurka-mediated phosphorylation of Plx1 (Xenopus Plk1 homologue) (Vigneron et al. 2018). In both Xenopus egg extracts (Vigneron et al. 2018) and cycling human cells (Gheghiani et al. 2017, Silva Cascales et al. 2021) activation of CCNA:CDK1 complexes precedes and stimulates the activation of PLK1, which precedes and stimulates the activation of CCNB:CDK1.
Literature References
PubMed ID Title Journal Year
27068477 Cdk1 Phosphorylates SPAT-1/Bora to Promote Plk1 Activation in C. elegans and Human Cells

Pintard, L, Van Hove, L, Martino, L, Joly, N, Panbianco, C, Gotta, M, Santamaria, A, Schwager, F, Tavernier, N, Thomas, Y, Cirillo, L

Cell Rep 2016
18521620 Plk1 regulates mitotic Aurora A function through betaTrCP-dependent degradation of hBora

Nigg, EA, Chan, EH, Santamaria, A, Silljé, HH

Chromosoma 2008
33402344 Cyclin A2 localises in the cytoplasm at the S/G2 transition to activate PLK1

Kuzin, V, Burdova, K, Middleton, A, Silva Cascales, H, Macurek, L, Müllers, E, Lindqvist, A, Baranello, L, Stoy, H

Life Sci Alliance 2021
16890155 Mitotic activation of the kinase Aurora-A requires its binding partner Bora

Hutterer, A, Zigman, M, Knoblich, JA, Schleiffer, A, Wirtz-Peitz, F, Berdnik, D

Dev. Cell 2006
Participants
Participates
Catalyst Activity

cyclin-dependent protein serine/threonine kinase activity of CCNB1,CCNB2:p-T161-CDK1 [cytosol]

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