Modulation of YBX1 Phosphorylation Determines Epidermal Stem Cell Function

The RNA-binding protein YBX1 regulates epidermal stem cell function. When YBX1 expression is lost in keratinocytes, there's a decrease in the proliferative potential of epidermal progenitors and alterations in all epidermal lineages. YBX1 binds the 3’UTR of multiple targets in epidermal stem cells, inhibiting the translation of senescence-associated cytokines and mediating stem cell self-renewal and proliferation. Phosphorylation of YBX1 can reduce its RNA binding affinity, and it's found that phosphorylated YBX1 is elevated in epidermal stem cells from donors of different ages. Small molecule inhibitors of PI3 kinase (PI3K), such as PI-103 and GDC-0941, can inhibit YBX1 phosphorylation levels, reducing cellular senescence in primary epidermal stem cells from adult donors. These inhibitors also increase the speed of epidermal wound closure in a wound healing model and epidermal regeneration model. This suggests that YBX1 is required to maintain epidermal regenerative potential.