Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated a gene (WS5) that is specifically expressed at the mRNA and protein level in avian fibroblasts transformed by the v-myc oncogene of avian acute leukemia virus MC29. In a conditional cell transformation system, WS5 gene expression was tightly correlated with v-myc activation. The WS5 gene contains 11 exons, encoding a 733-amino acid protein with a transmembrane region and a polycystic kidney disease (PKD) domain. Near the transcriptional start site, the WS5 promoter contains a cluster of four binding sites for the Myc-Max complex and a binding site for transcription factor C/EBPalpha. Electrophoretic mobility shift assays and chromatin immunoprecipitation showed that Myc, Max and C/EBPalpha bind specifically to these sites. Functional promoter analyses revealed that both the Myc-binding site cluster and the C/EBPalpha-binding site are essential for strong transcriptional activation, and that Myc and C/EBPalpha synergistically activate the WS5 promoter. Ectopic expression of WS5 led to cell transformation documented by anchorage-independent growth. The human melanoma antigen Pmel17, a type I transmembrane glycoprotein, is the mammalian protein with the highest amino acid sequence identity (38%) to WS5. The Pmel17 gene is regulated by the MITF protein, a bHLHZip transcription factor with DNA binding specificities similar to those of Myc/Max. WS5 is also related to human glycoprotein GPNMB expressed in metastatic melanoma cells and implicated in the progression of brain and liver tumors.
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PMID:WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential. 1696 80

Endothelin-1 (ET-1) plays an indispensable role in epidermal pigmentation in hyperpigmentary disorders due to a central role in melanogenesis. Nevertheless, precise mechanism involved in ET-1-induced hyperpigmentation is still undefined. Glycoprotein (transmembrane) non-metastatic melanoma protein b (GPNMB) is a key element in melanosome formation. Therefore, we speculated that GPNMB was correlated with ET-1-induced pigmentation. After culturing with ET-1, melanin synthesis was significantly up-regulated, accompanying with increased expression of GPNMB and microphthalmia- associated transcription factor (MITF). Total number of melanosomes and melanin synthesis were sharply reduced via GPNMB-siRNA transfection, indicating ET-1-induced pigmentation by GPNMB-dependent manner. Furthermore, MITFsiRNA transfection strikingly inhibited GPNMB expression and the melanogenesis, and this suppression failed to be alleviated by ET-1 stimulation. All of these results demonstrated that ET-1 can trigger melanogenesis via the MITF-regulated GPNMB pathway. Taken together, these findings will provide a new explanation of how ET-1 induces hyperpigmentation, and possibly supply a new strategy for cosmetic studies.
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PMID:Endothelin-1 enhances the melanogenesis via MITF-GPNMB pathway. 2388 3

To investigate whether ocular albinism type 1 (OA1) is differentially expressed in the skin of mice with different coat colors and to determine its correlation with coat color establishment in mouse, the expression patterns and tissue distribution characterization of OA1 in the skin of mice with different coat colors were qualitatively and quantitatively analyzed by real-time quantitative PCR (qRT-PCR), immunofluorescence staining and Western blot. The qRT-PCR analysis revealed that OA1 mRNA was expressed in all mice skin samples tested, with the highest expression level in brown skin, a moderate expression level in black skin and the lowest expression level in gray skin. Positive OA1 protein bands were also detected in all skin samples by Western blot analysis. The relative expression levels of OA1 protein in both black and brown skin were significantly higher than that in gray skin, but there was no significant difference between black and brown mice. Immunofluorescence assays revealed that OA1 was mainly expressed in the hair follicle matrix, the inner and outer root sheath in the skin tissues with different coat colors. To get further insight into the important role of OA1 in the melanocytes' pigmentation, we transfected the OA1 into mouse melanocytes and then detected the relative expression levels of pigmentation-related gene. Simultaneously, we tested the melanin content of melanocytes. As a result, the overexpression of OA1 significantly increased the expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TRP1) and premelanosome protein (PMEL). However, the tyrosinase-related protein 2 (TRP2) level was attenuated. By contrast, the level of glycoprotein non-metastatic melanoma protein b (GPNMB) was unaffected by OA1 overexpression. Furthermore, we observed a significant increase in melanin content in mouse melanocyte transfected OA1. Therefore, we propose that OA1 may participate in the formation of coat color by regulating the level of MITF and the number, size, motility and maturation of melanosome.
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PMID:Ocular Albinism Type 1 Regulates Melanogenesis in Mouse Melanocytes. 2769

Background: The mechanisms of Parkinson's disease (PD) include complicated genetic factors. The roles of newly found risk genes need to be further verified among different ethnicities. In a two-stage meta-analysis, single nucleotide polymorphism (SNP) of rs156429 in glycoprotein non-metastatic melanoma protein B (GPNMB) was reported to be associated with PD. So far clinical studies have focused on association between rs156429 and PD onset, however there is little evidence linking rs156429 with PD symptoms. Objective: This study aimed to investigate the possible association of GPNMB rs156429 with PD manifestations among southeastern Chinese people. Methods: Demographic variables, disease-related factors, and motor and non-motor assessments of 511 PD patients were collected. Polymerase chain reaction (PCR) and SNaPshot technique were used to detect GPNMB rs156429. The associations of rs156429 with PD rating scales and clinical manifestations were analyzed by Kruskal-Wallis test and logistic regression model separately. Results: Kruskal-Wallis test and logistic regression model failed to reveal an association between GPNMB rs156429 and scores from Montreal Cognitive Assessment (MoCA) (p = 0.037; p = 1.000 after correction), and pain symptoms of 511 PD patients (p = 0.008, OR = 0.59, 95% CI = 0.40-0.87, overdominant model after adjustment; p = 0.168 after correction, overdominant model after adjustment). However, further analysis based on genders showed that GPNMB rs156429 might have a trend for being associated with cognitive dysfunction (Mini-Mental State Examination (MMSE), p = 0.064 after correction; MoCA, p = 0.064 after correction) and pain symptoms (p = 0.063 after correction, overdominant model after adjustment) in female PD patients but not male patients. Conclusions: This study revealed that GPNMB rs156429 might have a trend for being associated with cognitive dysfunction and pain symptoms of female PD patients in the southeastern Chinese population. Further studies from a larger sample size are needed to confirm these findings.
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PMID:The Association Analysis of GPNMB rs156429 With Clinical Manifestations in Chinese Population With Parkinson's Disease. 3298 28