PMID- 29857961 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1873-569X (Electronic) IS - 0923-1811 (Linking) VI - 91 IP - 3 DP - 2018 Sep TI - The role of sex-determining region Y-box 6 in melanogenesis in alpaca melanocytes. PG - 268-275 LID - S0923-1811(18)30233-0 [pii] LID - 10.1016/j.jdermsci.2018.05.007 [doi] AB - BACKGROUND: Sex-determining region Y-box (SOX) proteins function as transcriptional regulators. The derivation of melanocytes from nerve crest cells has been reported to depend on SOX proteins, including SOX10 and SOX5. Whether SOX6 is expressed and has a functional role in melanocytes is unknown. OBJECTIVE: We aimed to study the effect of transcription factor SOX6 on melanogenesis in alpaca melanocytes. METHODS: We verified the role of SOX6 in melanogenesis by overexpressing and inhibiting SOX6 in melanocytes. Co-immunoprecipitation (co-IP) experiments were performed to further explore the function of SOX6 in melanogenesis and its mechanism of melanin production. We found that SOX6 interacted with cyclin-dependent kinase (CDK5), beta-catenin, and Cyclin D1. RESULTS: Bioinformatics analysis suggested that SOX6 has a phosphorylation site for CDK5, which regulates melanogenesis, suggesting that SOX6 might play a role in melanogenesis. Co-IP experiments indicated that SOX6 interacted with CDK5, beta-catenin, and Cyclin D1. Quantitative real-time polymerase chain reaction and western blot analyses of SOX6-overexpressing melanocytes revealed increased mRNA and protein expression of Cyclin D1, CDK5, microphthalmia transcription factor (MITF), tyrosinase (TYR), tyrosine related protein-1 (TYRP1), and dopachrome-tautomerase (DCT), whereas beta-catenin levels decreased in SOX6-overexpressing melanocytes. The opposite results were observed upon SOX6 knockdown. The melanin content was significantly increased or decreased, respectively, by SOX6 overexpression or knockdown. CONCLUSION: Our results suggest that SOX6 might enhance melanogenesis by binding with beta-catenin to increase Cyclin D1 and MITF expression. CI - Copyright (c) 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved. FAU - Du, Bin AU - Du B AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, China. FAU - Liu, Xuexian AU - Liu X AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, China. FAU - Zhang, Pengqian AU - Zhang P AD - Department of Ecology Research, Beijing Milu Ecological Research Center, Nanhaizi, Daxing District, Beijing, 102600, China. FAU - Zhang, Junzhen AU - Zhang J AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, China. FAU - Ji, Kaiyuan AU - Ji K AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, China. FAU - Hu, Shuaipeng AU - Hu S AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, China. FAU - Yang, Shanshan AU - Yang S AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, China. FAU - Liu, Bo AU - Liu B AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, China. FAU - Fan, Ruiwen AU - Fan R AD - College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, China. Electronic address: ruiwenfan@163.com. LA - eng PT - Journal Article DEP - 20180523 PL - Netherlands TA - J Dermatol Sci JT - Journal of dermatological science JID - 9011485 RN - 0 (Melanins) RN - 0 (Microphthalmia-Associated Transcription Factor) RN - 0 (SOXD Transcription Factors) RN - 0 (beta Catenin) RN - 136601-57-5 (Cyclin D1) RN - EC 2.7.11.1 (Cyclin-Dependent Kinase 5) SB - IM MH - Animals MH - Camelids, New World MH - Cells, Cultured MH - Cyclin D1/genetics/metabolism MH - Cyclin-Dependent Kinase 5/genetics/metabolism MH - Gene Expression Regulation MH - Melanins/*biosynthesis MH - Melanocytes/*metabolism MH - Microphthalmia-Associated Transcription Factor/genetics/metabolism MH - Phosphorylation MH - Protein Binding MH - SOXD Transcription Factors/genetics/*metabolism MH - beta Catenin/genetics/metabolism OTO - NOTNLM OT - CDK5 OT - Cyclin D1 OT - Melanocyte OT - Melanogenesis OT - SOX6 EDAT- 2018/06/03 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/06/03 06:00 PHST- 2018/03/08 00:00 [received] PHST- 2018/05/08 00:00 [revised] PHST- 2018/05/20 00:00 [accepted] PHST- 2018/06/03 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/06/03 06:00 [entrez] AID - S0923-1811(18)30233-0 [pii] AID - 10.1016/j.jdermsci.2018.05.007 [doi] PST - ppublish SO - J Dermatol Sci. 2018 Sep;91(3):268-275. doi: 10.1016/j.jdermsci.2018.05.007. Epub 2018 May 23.