Regulation of Melanophilin (Mlph) gene expression by the glucocorticoid receptor (GR)

Myung, Cheol Hwan; Lee, Ji Eun; Jo, Chan Song; Park, Jong Il; Hwang, Jae Sung

doi:10.1038/s41598-021-96276-w

Cited by 3 publications

(9 citation statements)

References 43 publications

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“…24,26,27 In previous work, we showed that GR regulates Mlph expression by binding to the Mlph promoter. 18 In addition, we confirmed that 16-kauren, a triterpene derived from natural products, inhibits only the expression of Mlph among the tripartite complex proteins in vitro. 19 The c-Jun N-terminal kinase (JNK) belongs to the mitogen-activated protein kinases (MAPKs) family, which also includes extracellular signalregulated kinases (ERK) and p38, and responds to various cytokines and environmental stressors.…”

supporting

confidence: 59%

“…In a previous study, we found that Mlph expression is specifically regulated by GR. 18 In this study, we demonstrate that 16-kauren regulates the expression of Mlph, a melanosome transport protein, through phosphorylation of GR via activation of JNK. To investigate the signalling mechanisms by which 16-kauren regulates Mlph expression, we treated melan-a melanocytes with 16-kauren and observed the phosphorylation of GR without any changes in GR expression (Figure 2).…”

Section: Discussionmentioning

confidence: 59%

“…23,24,26 We have previously reported that Mlph expression is regulated by GR through direct binding to the promoter, indicating a relationship between 16-kauren and GR in Mlph expression. 18,19 To determine whether 16-kauren affects GR activity, we first evaluated the protein expression of GR using western blotting and found that 16-kauren did not change GR expression (Figure 2A). Similarly, at the transcriptional level, 16-kauren had no effect on the expression of GR mRNA as measured by RT-PCR (Figure 2B).…”

Section: -Kauren Induced the Phosphorylation Of Grmentioning

confidence: 99%

“…Mlph has a mutation that does not produce harmful effects, unlike Rab27a and Myo Va 5 . In our previous study, Mlph expression is specifically regulated by the glucocorticoid receptor (GR) 18 …”

Section: Introductionmentioning

confidence: 99%

“…2,4,6,7 Mlph has a mutation that does not produce harmful effects, unlike Rab27a and Myo Va. 5 In our previous study, Mlph expression is specifically regulated by the glucocorticoid receptor (GR). 18 GR is a member of the nuclear receptor superfamily and is activated by agonists such as glucocorticoids, cortisol, and dexamethasone (Dex). 20 Cortisol, which is synthesized in the adrenal cortex, is secreted into blood vessels and functions as a stress hormone…”

mentioning

confidence: 99%

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Phosphorylation of glucocorticoid receptor induced by 16‐kauren‐2‐beta‐18, 19‐triol decreases expression of Melanophilin through JNK signalling

Myung

Hwang

2023

Experimental Dermatology

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Abstract16‐kauren‐2‐beta‐18, 19‐triol (16‐kauren) is a natural diterpenoid substance derived from Asteraceae psiadia punctulata, a small tropical shrub in Africa and Asia, and it can reduce Mlph expression without affecting the expression of Rab27a and MyoVa in melanocytes. Melanophilin (Mlph) is an important linker protein in the melanosome transport process. However, the signal transduction pathway for the regulation of Mlph expression has not been fully established. We examined the mechanism of 16‐kauren on Mlph expression. Murine melan‐a melanocytes were used for in vitro analysis. Western blot analysis, quantitative real‐time polymerase chain reaction, and luciferase assay were performed. The inhibition of Mlph expression by 16‐kauren‐2β‐18,19‐triol (16‐kauren) occurs through the JNK signal and is reversed following glucocorticoid receptor (GR) activation by dexamethasone (Dex). Especially, 16‐kauren activates JNK and c‐jun signalling, part of the MAPK pathway, with subsequent Mlph repression. When the JNK signal is weakened by siRNA, the inhibition of Mlph expression by 16‐kauren was not seen. JNK activation by 16‐kauren induces GR phosphorylation, which leads to Mlph repression. These results demonstrate that 16‐kauren regulates Mlph expression through the phosphorylation of GR via the JNK signalling pathway.

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supporting

confidence: 59%

Section: Discussionmentioning

confidence: 59%

Section: -Kauren Induced the Phosphorylation Of Grmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Phosphorylation of glucocorticoid receptor induced by 16‐kauren‐2‐beta‐18, 19‐triol decreases expression of Melanophilin through JNK signalling

Myung

Hwang

2023

Experimental Dermatology

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Whole-transcriptome sequencing reveals a melanin-related ceRNA regulatory network in the breast muscle of Xichuan black-bone chicken

Li,

et al. 2024

Poultry Science

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Association analysis of melanophilin (MLPH) gene expression and polymorphism with plumage color in quail

et al. 2023

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Abstract. We explore the relationship between the melanophilin (MLPH) gene and quail plumage color and provide a reference for subsequent quail plumage color breeding. In this experiment, real-time quantitative PCR (RT-qPCR) technology was used to analyze the relative mRNA expression levels of Korean quail (maroon) and Beijing white quail embryos at different developmental stages. Two single-nucleotide polymorphisms (SNPs) in the MLPH gene were screened based on the RNA-sequencing (RNA-Seq) data of skin tissues of Korean quail and Beijing white quail during the embryonic stage. Kompetitive allele-specific PCR (KASP) technology was used for genotyping in the resource population, and correlation analysis was carried out with the plumage color traits of quail. Finally, bioinformatics was used to predict the effects of these two SNPs on the structure and function of the encoded protein. The results showed that the expression level of the MLPH gene during embryonic development of Beijing white quail was significantly higher than that of Korean quail (P<0.01). The frequency distribution of the three genotypes (CC, CA and AA) of the Beijing white quail at the c.1807C > A mutation site was significantly different from that of the Korean quail (P<0.01). The frequency distribution of the three genotypes (GG, GA and AA) of the Beijing white quail at the c.2129G > A mutation site was significantly different from that of the Korean quail (P<0.01). And there was a significant correlation between the c.1807C > A mutation site and the white plumage phenotype. Bioinformatics showed that SNP1 (c.1807C > A) was a neutral mutation and that SNP2 (c.2129G > A) was a deleterious mutation. The prediction of protein conservation showed that the mutation sites of coding proteins R603S and G710D caused by SNP1 (c.1807C > A) and SNP2 (c.2129G > A) were highly conserved.

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Regulation of Melanophilin (Mlph) gene expression by the glucocorticoid receptor (GR)

Cited by 3 publications

References 43 publications

Phosphorylation of glucocorticoid receptor induced by 16‐kauren‐2‐beta‐18, 19‐triol decreases expression of Melanophilin through JNK signalling

Phosphorylation of glucocorticoid receptor induced by 16‐kauren‐2‐beta‐18, 19‐triol decreases expression of Melanophilin through JNK signalling

Whole-transcriptome sequencing reveals a melanin-related ceRNA regulatory network in the breast muscle of Xichuan black-bone chicken

Association analysis of melanophilin (MLPH) gene expression and polymorphism with plumage color in quail

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