Downregulation of ΔNp63α in keratinocytes by p14 ARF-mediated SUMO-conjugation and degradation

Maria Vivo, Antonella Di Costanzo, Paola Fortugno, Alessandra Pollice, Viola Calabrò, Girolama La Mantia

Research output: Contribution to journalArticle

Abstract

The tumor suppressor p14ARF inhibits cell growth in response to oncogenic stress in a p53-dependent and independent manner. However, new physiologic roles for ARF activation have been proposed. We have previously demonstrated that ARF interacts with p63, influencing its transcriptional activity. p63 is a member of the p53 family involved in skin and limb development, as well as in the homeostasis of mature epidermis. Here, we show that, in human keratinocytes, as well as in tumor-derived cell lines, ARF targets ΔNp63α, the most abundantly expressed p63 isoform, to proteasomal degradation by stimulating its sumoylation. Interestingly, we have observed an increase of ARF expression in differentiating keratinocytes, that is concomitant to the already described upregulation of SUMO2/3. Remarkably, we found that ΔNp63α is preferentially sumoylated by SUMo2, instead of SUMo1, and p14ARF increases the efficiency of this process.

Original languageEnglish
Pages (from-to)3545-3551
Number of pages7
JournalCell Cycle
Volume8
Issue number21
Publication statusPublished - Nov 1 2009

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Keywords

  • Keratinocyte differentiation
  • p14ARF
  • p63
  • Protein degradation
  • Sumoylation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Vivo, M., Di Costanzo, A., Fortugno, P., Pollice, A., Calabrò, V., & La Mantia, G. (2009). Downregulation of ΔNp63α in keratinocytes by p14 ARF-mediated SUMO-conjugation and degradation. Cell Cycle, 8(21), 3545-3551.