SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells
SMILE (small heterodimer partner-interacting leucine zipper protein) is a transcriptional corepressor that potently regulates various cellular processes such as metabolism and growth in numerous tissues. However, its regulatory role in skin tissue remains uncharacterized. Here, we demonstrated that...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| author | Xuan T. Truong Young-Seung Lee Thuy T. P. Nguyen Hyun-Jin Kim Sung-Hak Kim Changjong Moon Don-Kyu Kim Hueng-Sik Choi Tae-Il Jeon |
| author_facet | Xuan T. Truong Young-Seung Lee Thuy T. P. Nguyen Hyun-Jin Kim Sung-Hak Kim Changjong Moon Don-Kyu Kim Hueng-Sik Choi Tae-Il Jeon |
| author_sort | Xuan T. Truong |
| collection | DOAJ |
| description | SMILE (small heterodimer partner-interacting leucine zipper protein) is a transcriptional corepressor that potently regulates various cellular processes such as metabolism and growth in numerous tissues. However, its regulatory role in skin tissue remains uncharacterized. Here, we demonstrated that SMILE expression markedly decreased in human melanoma biopsy specimens and was inversely correlated with that of microphthalmia-associated transcription factor (MITF). During melanogenesis, α-melanocyte-stimulating hormone (α-MSH) induction of MITF was mediated by a decrease in SMILE expression in B16F10 mouse melanoma cells. Mechanistically, SMILE was regulated by α-MSH/cAMP/protein kinase A signaling and suppressed MITF promoter activity via corepressing transcriptional activity of the cAMP response element-binding protein. Moreover, SMILE overexpression significantly reduced α-MSH-induced MITF and melanogenic genes, thereby inhibiting melanin production in melanocytes. Conversely, SMILE inhibition increased the transcription of melanogenic genes and melanin contents. These results indicate that SMILE is a downstream effector of cAMP-mediated signaling and is a critical factor in the regulation of melanogenic transcription; in addition, they suggest a potential role of SMILE as a corepressor in skin pigmentation. |
| first_indexed | 2024-03-09T17:45:14Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:45:14Z |
| publishDate | 2022-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-228bbf615b864ee9bd4eeb7d6720e41a2023-11-24T11:13:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231509410.3390/ijms232315094SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 CellsXuan T. Truong0Young-Seung Lee1Thuy T. P. Nguyen2Hyun-Jin Kim3Sung-Hak Kim4Changjong Moon5Don-Kyu Kim6Hueng-Sik Choi7Tae-Il Jeon8Department of Animal Science, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Animal Science, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Animal Science, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Animal Science, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Animal Science, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Integrative Food, Bioscience, and Biotechnology, Chonnam National University, Gwangju 61186, Republic of KoreaSchool of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Animal Science, Chonnam National University, Gwangju 61186, Republic of KoreaSMILE (small heterodimer partner-interacting leucine zipper protein) is a transcriptional corepressor that potently regulates various cellular processes such as metabolism and growth in numerous tissues. However, its regulatory role in skin tissue remains uncharacterized. Here, we demonstrated that SMILE expression markedly decreased in human melanoma biopsy specimens and was inversely correlated with that of microphthalmia-associated transcription factor (MITF). During melanogenesis, α-melanocyte-stimulating hormone (α-MSH) induction of MITF was mediated by a decrease in SMILE expression in B16F10 mouse melanoma cells. Mechanistically, SMILE was regulated by α-MSH/cAMP/protein kinase A signaling and suppressed MITF promoter activity via corepressing transcriptional activity of the cAMP response element-binding protein. Moreover, SMILE overexpression significantly reduced α-MSH-induced MITF and melanogenic genes, thereby inhibiting melanin production in melanocytes. Conversely, SMILE inhibition increased the transcription of melanogenic genes and melanin contents. These results indicate that SMILE is a downstream effector of cAMP-mediated signaling and is a critical factor in the regulation of melanogenic transcription; in addition, they suggest a potential role of SMILE as a corepressor in skin pigmentation.https://www.mdpi.com/1422-0067/23/23/15094cAMPmelanogenesisMITFskin pigmentationSMILE |
| spellingShingle | Xuan T. Truong Young-Seung Lee Thuy T. P. Nguyen Hyun-Jin Kim Sung-Hak Kim Changjong Moon Don-Kyu Kim Hueng-Sik Choi Tae-Il Jeon SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells International Journal of Molecular Sciences cAMP melanogenesis MITF skin pigmentation SMILE |
| title | SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells |
| title_full | SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells |
| title_fullStr | SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells |
| title_full_unstemmed | SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells |
| title_short | SMILE Downregulation during Melanogenesis Induces MITF Transcription in B16F10 Cells |
| title_sort | smile downregulation during melanogenesis induces mitf transcription in b16f10 cells |
| topic | cAMP melanogenesis MITF skin pigmentation SMILE |
| url | https://www.mdpi.com/1422-0067/23/23/15094 |
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