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

Y-box binding protein (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 DNp63a, 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 downregulated during keratinocyte differentiation. DNp63a 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 DNp63a suggesting that YB-1 and DNp63a interplay can support keratinocyte proliferation and protect cells from apoptosis under genotoxic stress.