Chapter 21 p53 protein and the response of human skin to UV

p53 is a tumor suppressor gene and mutation of p53 is a frequent event in skin cancer. Wild-type p53 is expressed in keratinocytes and in the epidermis after UV irradiation. Wild-type p53 encodes for a 53-kDa phosphoprotein that plays a pivotal role in regulating cell growth and cell death. The wt-p53 gene is also called 'guardian of the genome', for its role in preventing the accumulation of genetic alterations, observed in cancer cells. An important environmental stress condition, which causes DNA damage and to which we are all exposed, is UV present in sunlight. Especially skin cells, of which the keratinocytes are most prevalent, are continuously exposed to UV. To protect themselves against these damaging effects, skin cells dispose over the following protection mechanisms: growth arrest, DNA repair and apoptosis. Growth arrest and DNA repair prevent replication of damaged DNA. When DNA cannot be repaired, cells go into apoptosis, which can be considered as a last escape mechanism. There are arguments that p53 protein plays a mediating role in these protective responses in human skin upon UV exposure. First of all, p53 protein accumulates in human skin cells in vitro and in human skin in vivo upon UV irradiation. Furthermore p53 protein binds to DNA and transactivates target genes upon UV, although the molecular events, which regulate this aspect of p53 protein activity, are only beginning to be described. Particularly the regulation of p53 activity in human skin after a physiological relevant UV irradiation dose remains largely unsolved. © 2001 Elsevier B.V. All rights reserved.