JNK suppresses melanogenesis by interfering with CREB-regulated transcription coactivator 3-dependent MITF expression

Kim, Jihye; Hong, Areum; Kim, Yo-Han; Yoo, Hanju; Kang, Sang‐Wook; Chang, Sung Eun; Song, Youngsup

doi:10.7150/thno.41502

Cited by 42 publications

(36 citation statements)

References 40 publications

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“…The transcriptional regulation of TYR protein is currently under research, and the basic helix-loop-helix factor (essential for melanocyte differentiation) encoded by the ophthalmopathy gene can pass through the M-box near the promoter and the E-box activates the TYR promoter 18 , 19 . MITF is a cell type-specific factor that can specifically activate the TYR gene's promoter activity through the CATGTG motif of the TYR distal element (TDE), which activates the transcription of the TYR gene.…”

Section: Discussionmentioning

confidence: 99%

“…Intense and intermittent sun exposure boosts the normal function of melanocytes, resulting in their proliferation and increasing melanin production. Cutaneous melanoma is related to intermittent and constant sun exposure 4 , 19 , 26 . This stimulation may occur because of increased synthesis of melanocyte stimulating hormone receptors, which is concurrent with the repair of DNA damage caused by sun radiation 27 .…”

Section: Discussionmentioning

confidence: 99%

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Salidroside can target both P4HB-mediated inflammation and melanogenesis of the skin

Ding¹,

Zhang²,

Jin³

et al. 2020

Theranostics

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Rationale: Many external factors can induce the melanogenesis and inflammation of the skin. Salidroside (SAL) is the main active ingredient of Rhodiola , which is a perennial grass plant of the Family Crassulaceae. This study evaluated the effect and molecular mechanism of SAL on skin inflammation and melanin production. It then explored the molecular mechanism of melanin production under ultraviolet (UV) and inflammatory stimulation. Methods: VISIA skin analysis imaging system and DermaLab instruments were used to detect the melanin reduction and skin brightness improvement rate of the volunteers. UV-treated Kunming mice were used to detect the effect of SAL on skin inflammation and melanin production. Molecular docking and Biacore were used to verify the target of SAL. Immunofluorescence, luciferase reporter assay, CO-IP, pull-down, Western blot, proximity ligation assay (PLA), and qPCR were used to investigate the molecular mechanism by which SAL regulates skin inflammation and melanin production. Results: SAL can inhibit the inflammation and melanin production of the volunteers. SAL also exerted a protective effect on the UV-treated Kunming mice. SAL can inhibit the tyrosinase (TYR) activity and TYR mRNA expression in A375 cells. SAL can also regulate the ubiquitination degradation of interferon regulatory factor 1 (IRF1) by targeting prolyl 4-hydroxylase beta polypeptide (P4HB) to mediate inflammation and melanin production. This study also revealed that IRF1 and upstream stimulatory factor 1 (USF1) can form a transcription complex to regulate TYR mRNA expression. IRF1 also mediated inflammatory reaction and TYR expression under UV- and lipopolysaccharide-induced conditions. Moreover, SAL derivative SAL-plus (1-(3,5-dihydroxyphenyl) ethyl-β-d-glucoside) showed better effect on inflammation and melanin production than SAL. Conclusion: SAL can inhibit the inflammation and melanogenesis of the skin by targeting P4HB and regulating the formation of the IRF1/USF1 transcription complex. In addition, SAL-plus may be a new melanin production and inflammatory inhibitor.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Salidroside can target both P4HB-mediated inflammation and melanogenesis of the skin

Ding¹,

Zhang²,

Jin³

et al. 2020

Theranostics

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show abstract

“…In addition to CREB phosphorylation by PKA, recent studies have demonstrated that the recruitment of CREB-regulated transcription coactivator (CRTC) 3 to the CREB transcription complex is also required for cAMP-stimulated MITF. MITF performs the most essential role in the regulation of melanin synthesis and the resultant transcription of melanogenic enzymes [ 26 , 40 , 41 ]. During this intracellular signaling process, melanogenesis is regulated by a key enzyme, tyrosinase, and additional enzymatic proteins, such as TRP-1 and DCT [ 1 , 2 , 3 , 4 ].…”

Section: Discussionmentioning

confidence: 99%

Carvedilol, an Adrenergic Blocker, Suppresses Melanin Synthesis by Inhibiting the cAMP/CREB Signaling Pathway in Human Melanocytes and Ex Vivo Human Skin Culture

Choi

Yoo

Lee

et al. 2020

IJMS

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Catecholamines function via G protein-coupled receptors, triggering an increase in intracellular levels of 3′,5′-cyclic adenosine monophosphate (cAMP) in various cells. Catecholamine biosynthesis and the β-adrenergic receptor exist in melanocytes; thus, catecholamines may play critical roles in skin pigmentation. However, their action and mechanisms mediating melanogenesis in human skin have not yet been investigated. Therefore, we examined the potential anti-melanogenetic effect of carvedilol, a nonselective β-blocker with weak α1-blocking activities. Carvedilol reduced melanin content and cellular tyrosinase activity without compromising cellular viability in normal human melanocytes as well as in mel-Ab immortalized mouse melanocytes. Carvedilol downregulated microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. Carvedilol treatment led to the downregulation of phosphor-cAMP response element-binding protein (CREB). Moreover, the increase in cAMP levels upon treatment with forskolin reversed the anti-melanogenic action of carvedilol. In addition, carvedilol remarkably reduced the melanin index in ultraviolet-irradiated human skin cultures. Taken together, our results indicate that carvedilol effectively suppresses melanogenesis in human melanocytes and ex vivo human skin by inhibiting cAMP/protein kinase A/CREB signaling. The anti-melanogenic effects of carvedilol have potential significance for skin whitening agents.

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“…MITF is regulated at transcription and multiple post-transcriptional levels. Its transcription in the melanocyte lineage is driven by SOX10, WNT/β-catenin and CREB, and is directly or indirectly suppressed by NF-κB, JNK, hedgehog, TGFβ, activated RhoA, HIF1α, Brn2/POU3F2 and ATF4 [ 2 , 3 , 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

RNA-seq Characterization of Melanoma Phenotype Switch in 3D Collagen after p38 MAPK Inhibitor Treatment

et al. 2021

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Melanoma phenotype plasticity underlies tumour dissemination and resistance to therapy, yet its regulation is incompletely understood. In vivo switching between a more differentiated, proliferative phenotype and a dedifferentiated, invasive phenotype is directed by the tumour microenvironment. We found that treatment of partially dedifferentiated, invasive A375M2 cells with two structurally unrelated p38 MAPK inhibitors, SB2021920 and BIRB796, induces a phenotype switch in 3D collagen, as documented by increased expression of melanocyte differentiation markers and a loss of invasive phenotype markers. The phenotype is accompanied by morphological change corresponding to amoeboid–mesenchymal transition. We performed RNA sequencing with an Illumina HiSeq platform to fully characterise transcriptome changes underlying the switch. Gene expression results obtained with RNA-seq were validated by comparing them with RT-qPCR. Transcriptomic data generated in the study will extend the present understanding of phenotype plasticity in melanoma and its contribution to invasion and metastasis.

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JNK suppresses melanogenesis by interfering with CREB-regulated transcription coactivator 3-dependent MITF expression

Cited by 42 publications

References 40 publications

Salidroside can target both P4HB-mediated inflammation and melanogenesis of the skin

Salidroside can target both P4HB-mediated inflammation and melanogenesis of the skin

Carvedilol, an Adrenergic Blocker, Suppresses Melanin Synthesis by Inhibiting the cAMP/CREB Signaling Pathway in Human Melanocytes and Ex Vivo Human Skin Culture

RNA-seq Characterization of Melanoma Phenotype Switch in 3D Collagen after p38 MAPK Inhibitor Treatment

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