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

TitleRegulation of cell cycle progression by forkhead transcription factor FOXO3 through its binding partner DNA replication factor Cdt1
Authors
Issue Date2012
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2012, v. 109, n. 15, p. 5717-5722 How to Cite?
AbstractTo 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.
Persistent Identifierhttp://hdl.handle.net/10722/292697
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, Yiru-
dc.contributor.authorXing, Yuqian-
dc.contributor.authorZhang, Lei-
dc.contributor.authorMei, Yang-
dc.contributor.authorYamamoto, Kazuo-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorYou, Han-
dc.date.accessioned2020-11-17T14:57:02Z-
dc.date.available2020-11-17T14:57:02Z-
dc.date.issued2012-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2012, v. 109, n. 15, p. 5717-5722-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/292697-
dc.description.abstractTo 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.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.titleRegulation of cell cycle progression by forkhead transcription factor FOXO3 through its binding partner DNA replication factor Cdt1-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1203210109-
dc.identifier.pmid22451935-
dc.identifier.pmcidPMC3326503-
dc.identifier.scopuseid_2-s2.0-84859582440-
dc.identifier.volume109-
dc.identifier.issue15-
dc.identifier.spage5717-
dc.identifier.epage5722-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000302533500037-
dc.identifier.issnl0027-8424-

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