Abstract
The keratinocytes in UV-irradiated skin produce and secrete α-melanocyte-stimulating hormone. α-Melanocyte-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.
| Original language | English |
|---|---|
| Pages (from-to) | 2459-2469 |
| Number of pages | 11 |
| Journal | Journal of Investigative Dermatology |
| Volume | 141 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2021 |
Bibliographical note
Funding Information:This study was supported by a 2016Research Grant from Kangwon National University, Chuncheon, Republic of Korea (Number 520160231) and Korea Basic Science Institute (National Research Facilities and Equipment Center; Daejeon, Republic of Korea) grant funded by the Ministry of Education (2019R1ABC1010020). We highly appreciate David E. Fisher (Department of Dermatology, Harvard Medical School, Boston, MA) for providing the MITF-responsive reporter plasmid pTRPM-1-wt. Conceptualization: DL, KJL, JHH; Data Curation: DL, KJL, JHH; Formal Analysis: DL, KJL; Funding Acquisition: JHH; Investigation: DL, KJL, MK, YK, HMJ, MJK, DHC, JC, KL, SK; Project Administration: KJL, JHH; Supervision: DK, JHH; Validation: DL, KJL, JHH; Visualization: DL, HMJ, KL, SK; Writing – Original Draft Preparation: DL, KJL, JHH; Writing – Review and Editing: KJL, JHH
Funding Information:
This study was supported by a 2016Research Grant from Kangwon National University , Chuncheon, Republic of Korea (Number 520160231) and Korea Basic Science Institute (National Research Facilities and Equipment Center; Daejeon, Republic of Korea) grant funded by the Ministry of Education (2019R1ABC1010020). We highly appreciate David E. Fisher (Department of Dermatology, Harvard Medical School, Boston, MA) for providing the MITF-responsive reporter plasmid pTRPM-1-wt.
Publisher Copyright:
© 2021 The Authors