title: SOX9 is a key player in ultraviolet B-induced melanocyte differentiation and pigmentation.
abstract: 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.
authors: Pigment Cell Biology Section, Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20814, USA.
authors: Thierry
authors: T
authors: Passeron
authors: Julio C
authors: JC
authors: Valencia
authors: Corine
authors: C
authors: Bertolotto
authors: Toshihiko
authors: T
authors: Hoashi
authors: Elodie
authors: E
authors: Le Pape
authors: Kaoruko
authors: K
authors: Takahashi
authors: Robert
authors: R
authors: Ballotti
authors: Vincent J
authors: VJ
authors: Hearing
mesh_terms: 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
chemical_list: D006609:High Mobility Group Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D014157:Transcription Factors; D000242:Cyclic AMP; D011494:Protein Kinases
references: Mol Cell Biol. 2000 Jun;20(11):4149-58
references: 10805756
references: Exp Cell Res. 2005 Aug 1;308(1):222-35
references: 15896776
references: J Biol Chem. 2000 Oct 6;275(40):30757-60
references: 10938265
references: Dev Biol. 2000 Nov 15;227(2):239-55
references: 11071752
references: J Biol Chem. 2000 Dec 1;275(48):37978-83
references: 10973953
references: Genes Dev. 2005 Sep 1;19(17):1980-5
references: 16140982
references: Front Biosci. 2006;11:733-42
references: 16146765
references: Peptides. 2005 Oct;26(10):1858-70
references: 16005546
references: J Eur Acad Dermatol Venereol. 2006 Aug;20(7):846-52
references: 16898909
references: Trends Mol Med. 2006 Sep;12(9):406-14
references: 16899407
references: Pigment Cell Res. 2000 Apr;13(2):60-9
references: 10841026
references: Nat Genet. 2000 Dec;26(4):490-4
references: 11101852
references: Brain Res. 2001 Jul 6;906(1-2):143-8
references: 11430871
references: J Biol Chem. 2001 Jul 27;276(30):28147-54
references: 11382753
references: Dev Dyn. 2001 Aug;221(4):373-9
references: 11500974
references: EMBO J. 2001 Sep 3;20(17):5022-31
references: 11532965
references: Dev Biol. 2001 Sep 15;237(2):245-57
references: 11543611
references: J Biol Chem. 2001 Sep 21;276(38):35390-5
references: 11423552
references: Oncogene. 2003 May 19;22(20):3024-34
references: 12789277
references: Pigment Cell Res. 2003 Aug;16(4):374-82
references: 12859621
references: Development. 2003 Dec;130(23):5681-93
references: 14522876
references: J Biol Chem. 2003 Nov 14;278(46):45224-30
references: 12944398
references: FEBS Lett. 2004 Jan 2;556(1-3):236-44
references: 14706856
references: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6502-7
references: 15096597
references: Hum Mol Genet. 2004 Jun 15;13(12):1213-8
references: 15115764
references: FASEB J. 2004 Jun;18(9):989-91
references: 15059972
references: Gene Ther. 2004 Jul;11(13):1033-9
references: 15164092
references: J Biol Chem. 2004 Jul 2;279(27):28330-8
references: 15096515
references: Pigment Cell Res. 2004 Aug;17(4):352-62
references: 15250937
references: Nature. 1994 Dec 8;372(6506):525-30
references: 7990924
references: Am J Hum Genet. 1995 Nov;57(5):1028-36
references: 7485151
references: J Endocrinol. 1995 Nov;147(2):R1-4
references: 7490543
references: J Cell Biol. 1996 Aug;134(3):747-55
references: 8707852
references: Mol Cell Biol. 1997 Apr;17(4):2336-46
references: 9121483
references: Nat Genet. 1997 Jun;16(2):174-8
references: 9171829
references: J Invest Dermatol. 1997 Jun;108(6):838-42
references: 9182807
references: Dev Biol. 1997 Dec 1;192(1):193-8
references: 9405108
references: Nat Genet. 1998 Feb;18(2):171-3
references: 9462749
references: Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7374-8
references: 9636156
references: J Biol Chem. 1998 Jul 31;273(31):19560-5
references: 9677380
references: J Cell Biol. 1998 Aug 10;142(3):827-35
references: 9700169
references: Anal Biochem. 1999 Jun 1;270(2):207-19
references: 10334838
references: Nature. 2005 Feb 17;433(7027):764-9
references: 15716956
references: Spine (Phila Pa 1976). 2005 Mar 15;30(6):625-30
references: 15770176
references: EMBO J. 2005 May 18;24(10):1798-809
references: 15889150
references: Exp Cell Res. 2007 Apr 1;313(6):1069-79
references: 17289023