The role of p53 in pigmentation, tanning and melanoma

• Published in: Pigment cell and melanoma research Vol. 21; no. 5; pp. 525 - 533
• Main Authors: Box, Neil F., Terzian, Tamara
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2008
• Subjects: apoptosis; Cell Transformation, Neoplastic; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Humans; Keratinocytes - cytology; Keratinocytes - physiology; Keratinocytes - radiation effects; Melanocytes - cytology; Melanocytes - physiology; Melanocytes - radiation effects; melanoma; Melanoma - pathology; Melanoma - physiopathology; Mutation; p53; pigmentation; progression; Proto-Oncogene Proteins c-mdm2 - genetics; Proto-Oncogene Proteins c-mdm2 - metabolism; Signal Transduction - physiology; skin; Skin Pigmentation - physiology; Skin Pigmentation - radiation effects; sunburn; Tumor Suppressor Protein p14ARF - genetics; Tumor Suppressor Protein p14ARF - metabolism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Ultraviolet Rays - adverse effects
• ISSN: 1755-1471; 1755-148X
• DOI: 10.1111/j.1755-148X.2008.00495.x

Summary p53 has a central role in skin pigmentation and may impact on melanoma at all stages, however, as it’s mutation frequency in melanoma is low, it’s role has been somewhat under‐appreciated. During normal skin function, p53 in the keratinocyte is a transducer of the skin tanning signal and an essential component of what is effectively a keratinocyte‐melanocyte signaling cycle that regulates skin pigmentation. It is clear that this cycle functions optimally in skin of dark pigmentation. When melanin biosynthesis is genetically disrupted in skin of white complexion, we propose that this cycle operates as a promoter of melanocyte proliferation. The cell autonomous function of p53 in melanocytes is not well described, however, the balance of the evidence suggests that p53 is an effective tumor suppressor and the myriad of mechanisms by which the p53 pathway may be dysregulated in tumors attests to it importance as a tumor suppressor. In this review, we outline the known mechanisms that impair p53 itself and its immediate regulators or target genes during melanomagenesis. Due to the importance of this pathway, it is clear that p53 disruptions may relate directly to a patient’s prognosis. This pathway will continue to be a focus of investigation, particularly with respect to targeted experimental chemotherapeutics.