p53 regulates ERK1/2/CREB cascadeviaa novel SASH1/MAP2K2 crosstalk to induce hyperpigmentation
Autor: | Jiawei Zeng, Hui Li, Qinghe Xing, Xing Zeng, Zhongshu Kuang, Huangchao Luo, Fujun Luan, Hongying Dai, Ding'an Zhou, Yan Li, Lin He, Yong He, Ke Wang, Jiangshu Ma, Mei Chen, Bei-zhong Liu, Shu Li |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
MAP Kinase Kinase 2 CREB Models Biological Melanocyte migration Dyschromatosis universalis hereditaria 03 medical and health sciences 0302 clinical medicine Hyperpigmentation ERK1/2/CREB cascade Cell Line Tumor medicine Humans SASH1‐MAP2K2 crosstalk Cyclic AMP Response Element-Binding Protein Extracellular Signal-Regulated MAP Kinases p53‐POMC‐MC1R cascade biology Chemistry Tumor Suppressor Proteins Point mutation Skin Diseases Genetic Original Articles Cell Biology medicine.disease Phenotype Cell biology Crosstalk (biology) HEK293 Cells 030104 developmental biology 030220 oncology & carcinogenesis Mutation biology.protein Molecular Medicine Phosphorylation Original Article RNA Interference Tumor Suppressor Protein p53 medicine.symptom Pigmentation Disorders Protein Binding Signal Transduction |
Zdroj: | Journal of Cellular and Molecular Medicine |
ISSN: | 1582-1838 |
DOI: | 10.1111/jcmm.13168 |
Popis: | 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. |
Databáze: | OpenAIRE |
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