A Basic Domain-Derived Tripeptide Inhibits MITF Activity by Reducing its Binding to the Promoter of Genes
- 주제(기타) Dermatology
- 설명문(일반) [Lim, Dongyoung; Lee, Kyoung-Jin; Kim, Yuri; Kim, Minseo; Ju, Hyun-Mi; Kim, Myoung-Ju; Hahn, Jang-Hee] Kangwon Natl Univ, Sch Med, Dept Anat & Cell Biol, Chunchon 24341, South Korea; [Choi, Dong-Hwa] Gyeonggido Business & Sci Accelerator, Bioctr, Suwon, South Korea; [Choi, Jiwon] Yonsei Univ, Coll Dent, Oral Canc Res Inst, Dept Oral Pathol, Seoul, South Korea; [Kim, Suree] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea; [Kang, Dongmin] Korea Basic Sci Inst, Western Seoul Ctr, Seoul, South Korea; [Lee, Kyoungyul] Kangwon Natl Univ, Sch Med, Dept Pathol, Chunchon, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Bronze
- 발행기관 ELSEVIER SCIENCE INC
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000183735
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.jid.2021.01.037
- PubMed https://pubmed.ncbi.nlm.nih.gov/33823181
초록/요약
The keratinocytes in UV-irradiated skin produce and secrete a-melanocyte-stimulating hormone. alpha-Melano-cyte-stimulating hormone upregulates the expression of MITF in melanocytes through the cAMP-protein kinase A-CREB signaling pathway. Thereafter, MITF induces the expression of melanogenic genes, including the tyrosinase gene TYR and TYRP-1 and TYRP-2 genes, which leads to the synthesis and accumulation of melanin. In this study, we examined whether MITF basic region-derived tripeptides can bind to the DNA-binding domain of MITF and inhibit MITF-induced melanogenesis through the inhibition of MITF-DNA binding. MITF-KGR, a representative MITF-derived tripeptide, suppressed the transcriptional activity of MITF by disrupting its binding to the promoter region of the target genes, which resulted in the inhibition of skin epidermis thickness and melanin synthesis in vivo and in vitro. Our results indicate that MITF-KGR exerts an inhibitory effect on melanogenesis by targeting MITF.
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