NF-Y Mediates the Transcriptional Inhibition of the cyclin B1, cyclin B2, and cdc25C Promoters upon Induced G2 Arrest

Isabella Manni, Giuseppina Mazzaro, Aymone Gurtner, Roberto Mantovani, Ulrike Haugwitz, Karen Krause, Kurt Engeland, Ada Sacchi, Silvia Soddu, Giulia Piaggio

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

During normal cell cycles, the function of mitotic cyclin-cdk1 complexes, as well as of cdc25C phosphatase, is required for G2 phase progression. Accordingly, the G2 arrest induced by DNA damage is associated with a down-regulation of mitotic cyclins, cdk1, and cdc25C phosphatase expression. We found that the promoter activity of these genes is repressed in the G2 arrest induced by DNA damage. We asked whether the CCAAT-binding NF-Y modulates mitotic cyclins, cdk1, and cdc25C gene transcription during this type of G2 arrest. In our experimental conditions, the integrity of the CCAAT boxes of cyclin B1, cyclin B2, and cdc25C promoters, as well as the presence of a functional NF-Y complex, is strictly required for the transcriptional inhibition of these promoters. Furthermore, a dominant-negative p53 protein, impairing doxorubicin-induced G2 arrest, prevents transcriptional down-regulation of the mitotic cyclins, cdk1, and cdc25C genes. We conclude that, as already demonstrated for cdk1, NF-Y mediates the transcriptional inhibition of the mitotic cyclins and the cdc25C genes during p53-dependent G2 arrest induced by DNA damage. These data suggest a transcriptional regulatory role of NF-Y in the G2 checkpoint after DNA damage.

Original languageEnglish
Pages (from-to)5570-5576
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number8
DOIs
Publication statusPublished - Feb 23 2001

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Cyclin B2
Cyclin B1
Cyclins
DNA Damage
cdc25 Phosphatases
Genes
DNA
Down-Regulation
G2 Phase
p53 Genes
Transcription
Doxorubicin
Cell Cycle
Cells

ASJC Scopus subject areas

  • Biochemistry

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NF-Y Mediates the Transcriptional Inhibition of the cyclin B1, cyclin B2, and cdc25C Promoters upon Induced G2 Arrest. / Manni, Isabella; Mazzaro, Giuseppina; Gurtner, Aymone; Mantovani, Roberto; Haugwitz, Ulrike; Krause, Karen; Engeland, Kurt; Sacchi, Ada; Soddu, Silvia; Piaggio, Giulia.

In: Journal of Biological Chemistry, Vol. 276, No. 8, 23.02.2001, p. 5570-5576.

Research output: Contribution to journalArticle

Manni, Isabella ; Mazzaro, Giuseppina ; Gurtner, Aymone ; Mantovani, Roberto ; Haugwitz, Ulrike ; Krause, Karen ; Engeland, Kurt ; Sacchi, Ada ; Soddu, Silvia ; Piaggio, Giulia. / NF-Y Mediates the Transcriptional Inhibition of the cyclin B1, cyclin B2, and cdc25C Promoters upon Induced G2 Arrest. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 8. pp. 5570-5576.
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AU - Gurtner, Aymone

AU - Mantovani, Roberto

AU - Haugwitz, Ulrike

AU - Krause, Karen

AU - Engeland, Kurt

AU - Sacchi, Ada

AU - Soddu, Silvia

AU - Piaggio, Giulia

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