Acetylation-enhanced Sp1 transcriptional activity suppresses Mlph expression
Abstract Melanosome transport is regulated by major proteins, including Rab27a, Melanophilin (Mlph), and Myosin Va (Myo-Va), that form a tripartite complex. Mutation of these proteins causes melanosome aggregation around the nucleus. Among these proteins, Mlph is a linker between Rab27a and Myo-Va....
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-86282-7 |
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| author | Chan Song Jo Hairu Zhao Jae Sung Hwang |
| author_facet | Chan Song Jo Hairu Zhao Jae Sung Hwang |
| author_sort | Chan Song Jo |
| collection | DOAJ |
| description | Abstract Melanosome transport is regulated by major proteins, including Rab27a, Melanophilin (Mlph), and Myosin Va (Myo-Va), that form a tripartite complex. Mutation of these proteins causes melanosome aggregation around the nucleus. Among these proteins, Mlph is a linker between Rab27a and Myo-Va. There are some studies about the regulation of Mlph transcriptional expression. However, its regulation by post-translational modifications remains unclear. In this study, inhibition of HDACs by SAHA and TSA disrupted melanosome transport, causing melanosome aggregation. Specifically, we identified a novel mechanism in which HDAC5 regulates Mlph expression via Sp1. Knockdown of HDAC5 increased the acetylation of Sp1 and the binding to the Mlph promoter, thereby modulating its expression. This study highlights the crucial role of HDAC5 in melanosome transport through its interaction with Sp1. These findings suggest that HDAC5-mediated deacetylation is pivotal in the post-translational modification of melanosome transport, providing insights into the molecular mechanisms underlying this process. |
| format | Article |
| id | doaj-art-dd6420e25ee54e408f21bb20fef3c507 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-dd6420e25ee54e408f21bb20fef3c5072025-01-19T12:23:53ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-025-86282-7Acetylation-enhanced Sp1 transcriptional activity suppresses Mlph expressionChan Song Jo0Hairu Zhao1Jae Sung Hwang2Department of Genetics and Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee UniversityDepartment of Genetics and Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee UniversityDepartment of Genetics and Biotechnology, Graduate School of Biotechnology, College of Life Sciences, Kyung Hee UniversityAbstract Melanosome transport is regulated by major proteins, including Rab27a, Melanophilin (Mlph), and Myosin Va (Myo-Va), that form a tripartite complex. Mutation of these proteins causes melanosome aggregation around the nucleus. Among these proteins, Mlph is a linker between Rab27a and Myo-Va. There are some studies about the regulation of Mlph transcriptional expression. However, its regulation by post-translational modifications remains unclear. In this study, inhibition of HDACs by SAHA and TSA disrupted melanosome transport, causing melanosome aggregation. Specifically, we identified a novel mechanism in which HDAC5 regulates Mlph expression via Sp1. Knockdown of HDAC5 increased the acetylation of Sp1 and the binding to the Mlph promoter, thereby modulating its expression. This study highlights the crucial role of HDAC5 in melanosome transport through its interaction with Sp1. These findings suggest that HDAC5-mediated deacetylation is pivotal in the post-translational modification of melanosome transport, providing insights into the molecular mechanisms underlying this process.https://doi.org/10.1038/s41598-025-86282-7Melanosome transportMelanophilinPost-translational modificationsAcetylationSp1HDAC5 |
| spellingShingle | Chan Song Jo Hairu Zhao Jae Sung Hwang Acetylation-enhanced Sp1 transcriptional activity suppresses Mlph expression Scientific Reports Melanosome transport Melanophilin Post-translational modifications Acetylation Sp1 HDAC5 |
| title | Acetylation-enhanced Sp1 transcriptional activity suppresses Mlph expression |
| title_full | Acetylation-enhanced Sp1 transcriptional activity suppresses Mlph expression |
| title_fullStr | Acetylation-enhanced Sp1 transcriptional activity suppresses Mlph expression |
| title_full_unstemmed | Acetylation-enhanced Sp1 transcriptional activity suppresses Mlph expression |
| title_short | Acetylation-enhanced Sp1 transcriptional activity suppresses Mlph expression |
| title_sort | acetylation enhanced sp1 transcriptional activity suppresses mlph expression |
| topic | Melanosome transport Melanophilin Post-translational modifications Acetylation Sp1 HDAC5 |
| url | https://doi.org/10.1038/s41598-025-86282-7 |
| work_keys_str_mv | AT chansongjo acetylationenhancedsp1transcriptionalactivitysuppressesmlphexpression AT hairuzhao acetylationenhancedsp1transcriptionalactivitysuppressesmlphexpression AT jaesunghwang acetylationenhancedsp1transcriptionalactivitysuppressesmlphexpression |