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 Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

To ensure genome stability, DNA must be replicated once and only once during each cell cycle. Cdt1 is tightly regulated to make sure that cells do not rereplicate their DNA. Multiple regulatory mechanisms operate to ensure degradation of Cdt1 in S phase. However, little is known about the positive regulators of Cdt1 under physiological conditions. Here we identify FOXO3 as a binding partner of Cdt1. FOXO3 forms a protein complex with Cdt1, which in turn blocks its interaction with DDB1 and PCNA. Conversely, FOXO3 depletion facilitated the proteolysis of Cdt1 in unperturbed cells. Intriguingly, FOXO3 deficiency resulted in impaired S-phase entry and reduced cell proliferation. We provide data that FOXO3 knockdown mimics Cdt1 down-regulation and affects G1/S transitions. Our results demonstrate a unique role of FOXO3 in binding to Cdt1 and maintaining its level required for cell cycle progression.

Regulation of cell cycle progression by forkhead transcription factor FOXO3 through its binding partner DNA replication factor Cdt1