English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Mitotic entry, a critical decision point for maintaining genetic stability, is governed by the cyclin B/Cyclin dependent kinase 1 (Cdc2) complex. In Xenopus oocytes and early embryos, accumulation of cyclin B activates Cdk1, which then phosphorylates and activates the positive regulator Cdc25 in an autocatalytic feedback loop. However, cyclin B levels do not increase as some human cells approach mitosis, and the key factors regulating Cdk1 activation in human cells are unknown. We report here that reducing cyclin A expression by RNA interference (RNAi) in primary human fibroblasts inhibited activation of Cdc25B and Cdc25C and dephosphorylation of Cdk1 on tyrosine (tyr) 15. These results were reproduced in U2-OS cells by inducing the expression of a dominant-negative (dn) mutant of Cdk2, the principal cyclin A binding partner. Cdk2-dn induction could inhibit Cdc25B activity and foster Cdk1 tyr phosphorylation within the S phase, temporally dissociating these events from Cdk1 activation at mitosis. In contrast, reducing Cdk1 expression delayed mitotic entry without markedly impairing Cdc25B or Cdc25C activity. These results suggest that cyclin A/Cdk2 complexes are key regulators of Cdc25 and Cdk1 activation in human cells. This pathway appears to be commonly deregulated in cancer.

Cyclin A/Cdk2 complexes regulate activation of Cdk1 and Cdc25 phosphatases in human cells