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p63 and p53: Collaborative Partners or Dueling Rivals?

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.701986

Keywords

p53; p63; tumor suppressor; oncogene; transcription factor; pioneer factor

Funding

  1. Open Access Fund of the Leibniz Association [R35 GM138120, T32 GM132066]

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p53 and p63, as transcription factors, regulate both shared and unique target genes to exert their tumor suppressive or oncogenic effects. The previous notion of strict competition between the two siblings needs to be reevaluated, as they can also collaborate towards a common goal.
The tumor suppressor p53 and its oncogenic sibling p63 (Delta Np63) direct opposing fates in tumor development. These paralog proteins are transcription factors that elicit their tumor suppressive and oncogenic capacity through the regulation of both shared and unique target genes. Both proteins predominantly function as activators of transcription, leading to a paradigm shift away from Delta Np63 as a dominant negative to p53 activity. The discovery of p53 and p63 as pioneer transcription factors regulating chromatin structure revealed new insights into how these paralogs can both positively and negatively influence each other to direct cell fate. The previous view of a strict rivalry between the siblings needs to be revisited, as p53 and p63 can also work together toward a common goal.

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