Transcriptional activation of tyrosinase and TRP-1 by p53 links UV irradiation to the protective tanning response.
We are exposed constantly to potentially harmful compounds and radiations. Complex adaptive protective responses have evolved to prevent such agents causing cellular damage, including potentially oncogenic mutation. The p53 tumour suppressor appears to have a role in co-ordinating such responses: it is activated by diverse insults and it acts as a transcriptional regulator of downstream genes that facilitate cellular adaptation. Ultraviolet (UV) light is a particularly potent inducer of p53 expression. In addition, UV light induces the production of melanin as a protection against further irradiation-induced damage. This study shows that the promoters of the genes coding for the enzymes crucial in melanin biosynthesis, namely tyrosinase and tyrosinase-related protein-1 (TRP-1), are activated by wild-type p53. Both promoters have p53-responsive elements and are activated in vivo in a dose-dependent manner by wild-type p53, as well as by the p53 homologues p73alpha and p63alpha.
Nylander
K
K
Department of Molecular and Cellular Pathology, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK. karin.nylander@pathol.umu.se
Bourdon
J C
JC
Bray
S E
SE
Gibbs
N K
NK
Kay
R
R
Hart
I
I
Hall
P A
PA
D001483:Base Sequence; D001665:Binding Sites; D004789:Enzyme Activation / Q000235:genetics; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000235:genetics* / Q000378:metabolism; D010088:Oxidoreductases; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays
D008543:Melanins; D008562:Membrane Glycoproteins; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D010088:Oxidoreductases; C489799:TYRP1 protein, human; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase