Cyclin E drives human keratinocyte growth into differentiation

Oncogene
Ana FreijeA Gandarillas

Abstract

Human epidermis is continuously exposed to environmental mutagenic hazard and is the most frequent target of human cancer. How the epidermis coordinates proliferation with differentiation to maintain homeostasis, even in hyperproliferative conditions, is unclear. For instance, overactivation of the proto-oncogene MYC in keratinocytes stimulates differentiation. Here we explore the cell cycle regulation as proliferating human keratinocytes commit to terminal differentiation upon loss of anchorage or overactivation of MYC. The S-phase of the cell cycle is deregulated as mitotic regulators are inhibited in the onset of differentiation. Experimental inhibition of mitotic kinase cdk1 or kinases of the mitosis spindle checkpoint Aurora B or Polo-like Kinase, triggered keratinocyte terminal differentiation. Furthermore, hyperactivation of the cell cycle by overexpressing the DNA replication regulator Cyclin E induced mitosis failure and differentiation. Inhibition of Cyclin E by shRNAs attenuated the induction of differentiation by MYC. In addition, we present evidence that Cyclin E induces DNA damage and the p53 pathway. The results provide novel clues for the mechanisms committing proliferative keratinocytes to differentiate, with i...Continue Reading

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Citations

Jun 23, 2012·PloS One·Manuel Rosa-GarridoAlberto Gandarillas
Apr 10, 2014·Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]·Andrea ArenzClaus Wittekindt
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Jan 24, 2016·The Journal of Investigative Dermatology·Stefan W StollJames T Elder
Dec 18, 2013·Experimental Dermatology·Marianna Trakala, Marcos Malumbres
Nov 23, 2013·Experimental Dermatology·Alberto Gandarillas, Ana Freije
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Apr 21, 2016·Experimental Dermatology·Talveen S PurbaRalf Paus
Jan 21, 2018·Cell Death and Differentiation·Alberto GandarillasNatalia Sanz-Gómez
Jan 15, 2019·Cell Cycle·Alberto GandarillasAna Freije
Jan 28, 2020·Journal of Cellular Physiology·Adam RichardsonKehinde Ross
Feb 12, 2017·Cell Death and Differentiation·Elisabetta PalazzoMaria I Morasso
Feb 23, 2020·Cell Death and Differentiation·Natalia Sanz-GómezAlberto Gandarillas
Jan 27, 2019·Scientific Reports·Pilar MollinedoJose L Fernandez-Luna
Jan 11, 2017·Journal of Cell Science·Marta N ShahbaziMirna Perez-Moreno
Oct 3, 2020·The Journal of Cell Biology·Rut MolinuevoAlberto Gandarillas
Oct 25, 2020·Oncogene·Isabel de PedroAlberto Gandarillas
Dec 5, 2020·Seminars in Cancer Biology·K J PientaS R Amend
Jun 25, 2021·Mechanisms of Ageing and Development·Chin Yee Ho, Oliver Dreesen

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