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p27Kip1 represses the Pitx2-mediated expression of p21Cip1 and regulates DNA replication during cell cycle progression

The tumor suppressor p21 regulates cell cycle progression and peaks at mid/late G[sub.1]. However, the mechanisms regulating its expression during cell cycle are poorly understood. We found that embryonic fibroblasts from p27 null mice at early passages progress slowly through the cell cycle. These... Full description

Journal Title: Oncogene 2016
Main Author: E Gallastegui
Other Authors: A Biçer , S Orlando , A Besson , M J Pujol , O Bachs
Format: Electronic Article Electronic Article
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ID: ISSN: 0950-9232 ; E-ISSN: 1476-5594 ; DOI: 10.1038/onc.2016.200
Link: http://dx.doi.org/10.1038/onc.2016.200
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recordid: nature_a10.1038/onc.2016.200
title: p27Kip1 represses the Pitx2-mediated expression of p21Cip1 and regulates DNA replication during cell cycle progression
format: Article
creator:
  • E Gallastegui
  • A Biçer
  • S Orlando
  • A Besson
  • M J Pujol
  • O Bachs
subjects:
  • Cell Cycle – Research
  • DNA Replication – Research
  • Gene Expression – Research
  • Cancer Genetics – Research
ispartof: Oncogene, 2016
description: The tumor suppressor p21 regulates cell cycle progression and peaks at mid/late G[sub.1]. However, the mechanisms regulating its expression during cell cycle are poorly understood. We found that embryonic fibroblasts from p27 null mice at early passages progress slowly through the cell cycle. These cells present an elevated basal expression of p21 suggesting that p27 participates to its repression. Mechanistically, we found that p27 represses the expression of Pitx2 (an activator of p21 expression) by associating with the ASE-regulatory region of this gene together with an E2F4 repressive complex. Furthermore, we found that Pitx2 binds to the p21 promoter and induces its transcription. Finally, silencing Pitx2 or p21 in proliferating cells accelerates DNA replication and cell cycle progression. Collectively, these results demonstrate an unprecedented connection between p27, Pitx2 and p21 relevant for the regulation of cell cycle progression and cancer and for understanding human pathologies associated with p27 germline mutations. Oncogene (2017) 36, 350-361; doi: 10.1038/onc.2016.200; published online 6 June 2016
language:
source:
identifier: ISSN: 0950-9232 ; E-ISSN: 1476-5594 ; DOI: 10.1038/onc.2016.200
fulltext: fulltext
issn:
  • 0950-9232
  • 09509232
  • 1476-5594
  • 14765594
url: Link


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titlep27Kip1 represses the Pitx2-mediated expression of p21Cip1 and regulates DNA replication during cell cycle progression
creatorE Gallastegui ; A Biçer ; S Orlando ; A Besson ; M J Pujol ; O Bachs
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descriptionThe tumor suppressor p21 regulates cell cycle progression and peaks at mid/late G[sub.1]. However, the mechanisms regulating its expression during cell cycle are poorly understood. We found that embryonic fibroblasts from p27 null mice at early passages progress slowly through the cell cycle. These cells present an elevated basal expression of p21 suggesting that p27 participates to its repression. Mechanistically, we found that p27 represses the expression of Pitx2 (an activator of p21 expression) by associating with the ASE-regulatory region of this gene together with an E2F4 repressive complex. Furthermore, we found that Pitx2 binds to the p21 promoter and induces its transcription. Finally, silencing Pitx2 or p21 in proliferating cells accelerates DNA replication and cell cycle progression. Collectively, these results demonstrate an unprecedented connection between p27, Pitx2 and p21 relevant for the regulation of cell cycle progression and cancer and for understanding human pathologies associated with p27 germline mutations. Oncogene (2017) 36, 350-361; doi: 10.1038/onc.2016.200; published online 6 June 2016
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