ΔNp63α controls YB-1 protein stability: evidence on YB-1 as a new player in keratinocyte differentiation

Genes Cells. 2016 Jun;21(6):648-60. doi: 10.1111/gtc.12373. Epub 2016 May 11.

Abstract

Y-box binding protein 1 (YBX-1 or YB-1) is an oncoprotein that promotes replicative immortality, tumor cell invasion and metastasis. The increase in the abundance of YB-1 in the cell or YB-1 translocation from the cytoplasm to the nucleus is characteristic of malignant cell growth. We have previously reported that ΔNp63α, a transcription factor that is known to play a pivotal role in keratinocyte proliferation and differentiation, promotes YB-1 nuclear accumulation. Here, we show that YB-1 is highly expressed in proliferating keratinocytes and is down-regulated during keratinocyte differentiation. ΔNp63α reduces YB-1 protein turnover and leads to accumulation of ubiquitin-conjugated YB-1 into the nucleus. Reduction of YB-1 protein level, following treatment with a DNA-damaging agent, is inhibited by ΔNp63α suggesting that YB-1 and ΔNp63α interplay can support keratinocyte proliferation and protect cells from apoptosis under genotoxic stress.

MeSH terms

  • Cell Cycle
  • Cell Differentiation
  • Cell Line, Tumor
  • Down-Regulation
  • Humans
  • Keratinocytes / cytology*
  • Keratinocytes / metabolism
  • Protein Stability
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / metabolism*
  • Y-Box-Binding Protein 1 / chemistry*
  • Y-Box-Binding Protein 1 / metabolism

Substances

  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Y-Box-Binding Protein 1
  • YBX1 protein, human