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p38α MAPK is required for contact inhibition

Abstract

Proliferation of nontransformed cells is regulated by cell–cell contacts, which are referred to as contact-inhibition. Despite its generally accepted importance for cell cycle control, knowledge about the intracellular signalling pathways involved in contact inhibition is scarce. In the present work we show that p38α mitogen-activated protein kinase (MAPK) is involved in the growth-inhibitory signalling cascade of contact inhibition in fibroblasts. p38α activity is increased in confluent cultures of human fibroblasts compared to proliferating cultures. Time course studies show a sustained activation of p38α in response to cell–cell contacts in contrast to a transient activation after serum stimulation. The induction of contact inhibition by addition of glutaraldehyde-fixed cells is impaired by pharmacological inhibition of p38 as well as in p38α−/− fibroblasts. Further evidence for a central role of p38α in contact inhibition comes from the observation that p38α−/− fibroblasts show a higher saturation density compared to wild-type (wt) fibroblasts, which is reversed by reconstituted expression of p38α. In agreement with a defect in contact inhibition, p27Kip1 accumulation is impaired in p38α−/− fibroblasts compared to wt fibroblasts. Hence, our work shows a new role for p38α in contact inhibition and provides a mechanistic basis for the recently proposed tumour suppressive function of this MAPK pathway.

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Acknowledgements

The expert technical assistance of Sandra Niemann and Emma Black is gratefully acknowledged. This work was supported by the Grant Di 793/1-2 by the Deutsche Forschungsgemeinschaft (CD), by a grant by the Stiftung Rheinland-Pfalz für Innovation (8312-386261/539) and by a grant of the Fundacion Cientifica de la Asociacion Española Contra el Cancer (ARN).

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Correspondence to Cornelia Dietrich.

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Faust, D., Dolado, I., Cuadrado, A. et al. p38α MAPK is required for contact inhibition. Oncogene 24, 7941–7945 (2005). https://doi.org/10.1038/sj.onc.1208948

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Keywords

  • contact inhibition
  • p38 MAPK
  • fibroblasts

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