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p53 regulates ERK1/2/CREB cascade via a novel SASH1/MAP2K2 crosstalk to induce hyperpigmentation.

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机构： [a]Clinical Research Center, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China [b]Yongchuan Hospital, Chongqing Medical University, Chongqing, China [c]Children’s Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China [d]Dujiangyan People’s Hospital, Cheng du, Sichuan, China [e]Department of Nephrology and Rheumatology, the First People’s Hospital, Chenzhou, Hunan, China [f]Bio-X Institute, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China

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We previously reported that three point mutations in SASH1 and mutated SASH1 promote melanocyte migration in dyschromatosis universalis hereditaria (DUH) and a novel p53/POMC/Gαs/SASH1 autoregulatory positive feedback loop is regulated by SASH1 mutations to induce pathological hyperpigmentation phenotype. However, the underlying mechanism of molecular regulation to cause this hyperpigmentation disorder still remains unclear. In this study, we aimed to investigate the molecular mechanism undergirding hyperpigmentation in the dyschromatosis disorder. Our results revealed that SASH1 binds with MAP2K2 and is induced by p53-POMC-MC1R signal cascade to enhance the phosphorylation level of ERK1/2 and CREB. Moreover, increase in phosphorylated ERK1/2 and CREB levels and melanogenesis-specific molecules is induced by mutated SASH1 alleles. Together, our results suggest that a novel SASH1/MAP2K2 crosstalk connects ERK1/2/CREB cascade with p53-POMC-MC1R cascade to cause hyperpigmentation phenotype of DUH. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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出版当年[2017]版：

大类 | 2 区医学

小类 | 2 区医学：研究与实验 3 区细胞生物学

最新[2025]版：

大类 | 3 区医学

小类 | 3 区细胞生物学 3 区医学：研究与实验

第一作者：

第一作者机构： [a]Clinical Research Center, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China [b]Yongchuan Hospital, Chongqing Medical University, Chongqing, China [c]Children’s Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China

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通讯机构： [a]Clinical Research Center, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China [b]Yongchuan Hospital, Chongqing Medical University, Chongqing, China [c]Children’s Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China

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