Kalliopi Gkouskou

Publications (2)15.13 Total impact

• Source

  Available from: Alexandros G Georgakilas

  Article: Cdc6 expression represses E-cadherin transcription and activates adjacent replication origins.

  Maria Sideridou, Roubini Zakopoulou, Konstantinos Evangelou, Michalis Liontos, Athanassios Kotsinas, Emmanouil Rampakakis, Sarantis Gagos, Kaoru Kahata, Kristina Grabusic, Kalliopi Gkouskou, Ioannis P Trougakos, Evangelos Kolettas, Alexandros G Georgakilas, Sinisa Volarevic, Aristides G Eliopoulos, Maria Zannis-Hadjopoulos, Aristidis Moustakas, Vassilis G Gorgoulis
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  ABSTRACT: E-cadherin (CDH1) loss occurs frequently in carcinogenesis, contributing to invasion and metastasis. We observed that mouse and human epithelial cell lines overexpressing the replication licensing factor Cdc6 underwent phenotypic changes with mesenchymal features and loss of E-cadherin. Analysis in various types of human cancer revealed a strong correlation between increased Cdc6 expression and reduced E-cadherin levels. Prompted by these findings, we discovered that Cdc6 repressed CDH1 transcription by binding to the E-boxes of its promoter, leading to dissociation of the chromosomal insulator CTCF, displacement of the histone variant H2A.Z, and promoter heterochromatinization. Mutational analysis identified the Walker B motif and C-terminal region of Cdc6 as essential for CDH1 transcriptional suppression. Strikingly, CTCF displacement resulted in activation of adjacent origins of replication. These data demonstrate that Cdc6 acts as a molecular switch at the E-cadherin locus, linking transcriptional repression to activation of replication, and provide a telling example of how replication licensing factors could usurp alternative programs to fulfill distinct cellular functions.
  The Journal of Cell Biology 12/2011; 195(7):1123-40. · 10.26 Impact Factor
• Article: Tpl2 kinase signal transduction in inflammation and cancer.

  Maria Vougioukalaki, Dimitris C Kanellis, Kalliopi Gkouskou, Aristides G Eliopoulos
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  ABSTRACT: The activation of mitogen-activated protein kinases (MAPKs) is critically involved in inflammatory and oncogenic events. Tumor progression locus 2 (Tpl2), also known as COT and MAP3 kinase 8 (MAP3K8), is a serine-threonine kinase with an important physiological role in tumor necrosis factor, interleukin-1, CD40, Toll-like receptor and G protein-coupled receptor-mediated ERK MAPK signaling. Whilst the full characterization of the biochemical events that lead to the activation of Tpl2 still represent a major challenge, genetic and molecular evidence has highlighted interesting interactions with the NF-κB network. Here, we provide an overview of the multifaceted functions of Tpl2 and the molecular mechanisms that govern its regulation.
  Cancer letters 03/2011; 304(2):80-9. · 4.86 Impact Factor