title: Involvement of Nurr-1/Nur77 in corticotropin-releasing factor/urocortin1-induced tyrosinase-related protein 1 gene transcription in human melanoma HMV-II cells.
abstract: Recent molecular and biochemical analyses have revealed the presence of corticotropin-releasing factor (CRF) and urocortin (Ucn), together with their corresponding receptors in mammalian skin. The melanosomal enzyme tyrosinase-related protein 1 (TRP1) is involved in modulation of pigment production in response to stressors. Although CRF and Ucn are thought to have potent effects on the skin system, their possible roles and regulation have yet to be fully determined. This study aimed to explore the effects of CRF and Ucn on TRP1 gene expression using human melanoma HMV-II cells. The mRNA of CRF, Ucn1, Ucn2, and CRF receptor type 1 (CRF1 receptor) was detected in HMV-II cells. CRF and Ucn1 stimulated TRP1 gene transcription via the CRF1 receptor, and increased both Nurr-1 and Nur77 mRNA expression levels. Both CRF- and Ucn1-induced Nurr-1/Nur77 acted via a NGFI-B response element on the TRP1 promoter. The combination of Nurr-1/Nur77 and microphthalmia-associated transcription factor, a melanocyte-specific transcription factor gene induced by α-melanocyte-stimulating hormone, had additive effects on activation of TRP1 gene transcription. The findings suggest that in human melanoma HMV-II cells both CRF and Ucn1 regulate TRP1 gene expression via Nurr-1/Nur77 production, independent of pro-opiomelanocortin or α-melanocyte-stimulating hormone stimulation.
authors: Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors: Yutaka
authors: Y
authors: Watanuki
authors: Shinobu
authors: S
authors: Takayasu
authors: Kazunori
authors: K
authors: Kageyama
authors: Yasumasa
authors: Y
authors: Iwasaki
authors: Satoru
authors: S
authors: Sakihara
authors: Ken
authors: K
authors: Terui
authors: Takeshi
authors: T
authors: Nigawara
authors: Toshihiro
authors: T
authors: Suda
mesh_terms: D045744:Cell Line, Tumor; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008545:Melanoma; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000378:metabolism*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics / Q000378:metabolism*; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D014158:Transcription, Genetic; D054832:Urocortins / Q000235:genetics / Q000378:metabolism*; D000521:alpha-MSH; D000099052:CRF Receptor, Type 1
chemical_list: D008562:Membrane Glycoproteins; C539821:NR4A1 protein, human; C539882:NR4A2 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C576814:UCN protein, human; D054832:Urocortins; D000521:alpha-MSH; D000099052:CRF Receptor, Type 1; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone; D010088:Oxidoreductases; C489799:TYRP1 protein, human