Cdc7 kinase stimulates Aurora B kinase in M-phase.
Animals
Aurora Kinase B
/ metabolism
Cell Cycle
Cell Cycle Proteins
/ metabolism
Cell Division
Cell Line, Tumor
Centromere
/ metabolism
Chromosomal Proteins, Non-Histone
/ metabolism
HCT116 Cells
HEK293 Cells
HeLa Cells
Humans
Insecta
Mitosis
Mutation
Phosphorylation
Protein Serine-Threonine Kinases
/ metabolism
Rats
Spindle Apparatus
/ metabolism
Survivin
/ metabolism
Threonine
/ chemistry
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 12 2019
09 12 2019
Historique:
received:
27
09
2017
accepted:
16
08
2019
entrez:
11
12
2019
pubmed:
11
12
2019
medline:
16
12
2020
Statut:
epublish
Résumé
The conserved serine-threonine kinase, Cdc7, plays a crucial role in initiation of DNA replication by facilitating the assembly of an initiation complex. Cdc7 is expressed at a high level and exhibits significant kinase activity not only during S-phase but also during G2/M-phases. A conserved mitotic kinase, Aurora B, is activated during M-phase by association with INCENP, forming the chromosome passenger complex with Borealin and Survivin. We show that Cdc7 phosphorylates and stimulates Aurora B kinase activity in vitro. We identified threonine-236 as a critical phosphorylation site on Aurora B that could be a target of Cdc7 or could be an autophosphorylation site stimulated by Cdc7-mediated phosphorylation elsewhere. We found that threonines at both 232 (that has been identified as an autophosphorylation site) and 236 are essential for the kinase activity of Aurora B. Cdc7 down regulation or inhibition reduced Aurora B activity in vivo and led to retarded M-phase progression. SAC imposed by paclitaxel was dramatically reversed by Cdc7 inhibition, similar to the effect of Aurora B inhibition under the similar situation. Our data show that Cdc7 contributes to M-phase progression and to spindle assembly checkpoint most likely through Aurora B activation.
Identifiants
pubmed: 31819079
doi: 10.1038/s41598-019-54738-2
pii: 10.1038/s41598-019-54738-2
pmc: PMC6901529
doi:
Substances chimiques
Birc5 protein, rat
0
Cell Cycle Proteins
0
Chromosomal Proteins, Non-Histone
0
Survivin
0
Threonine
2ZD004190S
CDC7 protein, human
EC 2.7.1.-
AURKB protein, human
EC 2.7.11.1
Aurkb protein, rat
EC 2.7.11.1
Aurora Kinase B
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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