Abstract
Keratin 17 (K17) is a cytoskeletal protein that is part of the intermediate filaments in epidermal keratinocytes. In Krt17-/- mice, ionizing radiation (IR) induced more severe hair follicle damage, whereas the epidermal inflammatory response was attenuated as compared with wild-type (WT) mice. Both p53 and Krt17 have a major impact on global gene expression, as over 70% of the differentially expressed genes in the skin of WT mice showed no expression change in p53-/- or Krt17-/- skin post-IR. K17 does not interfere with the dynamics of p53 activation; rather, global p53-binding in the genome is altered in Krt17-/- mice. The absence of K17 leads to aberrant cell cycle progression and mitotic catastrophe in epidermal keratinocytes, which is due to the nuclear retention thus reduced degradation of B-Myb, a key regulator of the G2/M cell cycle transition. These results expand our understanding of the role of K17 in regulating global gene expression and IR-induced skin damage.