SOX9 is a key player in ultraviolet B-induced melanocyte differentiation and pigmentation.
SOX (SRY type HMG box) proteins are transcription factors that are predominantly known for their roles during development. During melanocyte development from the neural crest, SOX10 regulates microphthalmia-associated transcription factor, which controls a set of genes critical for pigment cell development and pigmentation, including dopachrome tautomerase and tyrosinase. We report here that another SOX factor, SOX9, is expressed by melanocytes in neonatal and adult human skin and is up-regulated by UVB exposure. We demonstrate that this regulation is mediated by cAMP and protein kinase. We also show that agouti signal protein, a secreted factor known to decrease pigmentation, down-regulates SOX9 expression. In adult and neonatal melanocytes, SOX9 regulates microphthalmia-associated transcription factor, dopachrome tautomerase, and tyrosinase promoters, leading to an increase in the expression of these key melanogenic proteins and finally to a stimulation of pigmentation. SOX9 completes the complex and tightly regulated process leading to the production of melanin by acting at a very upstream level. This role of SOX9 in pigmentation emphasizes the poorly understood impact of SOX proteins in adult tissues.
Passeron
Thierry
T
Pigment Cell Biology Section, Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA.
Valencia
Julio C
JC
Bertolotto
Corine
C
Hoashi
Toshihiko
T
Le Pape
Elodie
E
Takahashi
Kaoruko
K
Ballotti
Robert
R
Hearing
Vincent J
VJ
D002454:Cell Differentiation; D000242:Cyclic AMP / Q000502:physiology; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006609:High Mobility Group Proteins / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D008544:Melanocytes / Q000166:cytology* / Q000502:physiology* / Q000528:radiation effects; D011494:Protein Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor; D012880:Skin Pigmentation / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D014466:Ultraviolet Rays
D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D014157:Transcription Factors; D000242:Cyclic AMP; D011494:Protein Kinases
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