Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MSG1 is a nuclear protein and a possible transcriptional transactivator that is expressed strongly in melanocytes but very weakly, if at all, in most nonmelanocytic cells or adult mouse tissues. This strong expression of MSG1 in cultured normal human epidermal melanocytes was found to be dependent on both endothelin-1 and FGF-2. The phorbol ester TPA could be substituted for endothelin-1. The MSG1 mRNA transcripts were rapidly induced by either endothelin-1 or TPA. However, FGF-2 had no effects at the mRNA level, suggesting its contribution at the translational and/or posttranslational level(s). MSG1 (as well as its mRNA transcripts) was induced by TPA in human melanoma cells, which produce FGF-2 as an autocrine growth factor. Melanoma cells derived from primary tumors or tyrosinase-positive metastatic melanoma cells expressed MSG1 after TPA treatment, while tyrosinase-negative metastatic melanoma cells or nonmelanocytic cells did not. This TPA-induced MSG1 expression in melanoma cells correlated with the expression of the MSG1 mRNA transcripts and TPA-dependent transcriptional activation of the MSG1 promoter sequence, indicating its transcriptional regulation. In vivo, MSG1 protein was detected in human nevocytic nevus confined to the pigmented region, while MSG1 expression showed cell-level heterogeneity in pigmented melanoma tissues. These results demonstrate that MSG1 expression is regulated transcriptionally and posttranscriptionally by local growth factors as well as by the cellular status of differentiation.
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PMID:Regulation of expression of MSG1 melanocyte-specific nuclear protein in human melanocytes and melanoma cells. 968 35

Congenital defects in retinal pigmentation, as in oculocutaneous albinism Type I (OCA1), where tyrosinase is defective, result in visual abnormalities affecting the retina and pathways into the brain. Transgenic animals expressing a functional tyrosinase gene on an albino genetic background display a correction of all these abnormalities, implicating a functional role for tyrosinase in normal retinal development. To address the function of tyrosinase in the development of the mammalian visual system, we have generated a transgenic mouse model with inducible expression of the tyrosinase gene using the tetracycline (TET-ON) system. We have produced two types of transgenic mice: first, mice expressing the transactivator rtTA chimeric protein under the control of mouse tyrosinase promoter and its locus control region (LCR), and; second, transgenic mice expressing a mouse tyrosinase cDNA construct driven by a minimal promoter inducible by rtTA in the presence of doxycycline. Inducible experiments have been carried out with selected double transgenic mouse lines. Tyrosinase expression has been induced from early embryo development and its impact assessed with histological and biochemical methods in heterozygous and homozygous double transgenic individuals. We have found an increase of tyrosinase activity in the eyes of induced animals, compared with littermate controls. However, there was significant variability in the activation of this gene, as reported in analogous experiments. In spite of this, we could observe corrected uncrossed chiasmatic pathways, decreased in albinism, in animals induced from their first gestational week. These mice could be instrumental in revealing the role of tyrosinase in mammalian visual development.
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PMID:A transgenic mouse model with inducible Tyrosinase gene expression using the tetracycline (Tet-on) system allows regulated rescue of abnormal chiasmatic projections found in albinism. 1525 Sep 38

Restricted replication-competent adenoviruses (RRCAs) using tumor- and tissue-specific promoters (ttsP's) are new tools for cancer gene therapy. In this study we investigated viral and nonviral factors affecting "leakiness" of several ttsP's and their relevance for nonspecific ttsP-dependent RRCA (ttsP-RRCA) replication. The leakiness of the ttsP's in nontarget cells was per se highly variable and correlated with levels of nonspecific ttsP-RRCA replication. Transcriptional regulator elements fused to ttsP's showed variable effects: a hypoxic response element reduced leakiness of an alpha-fetoprotein promoter. In contrast, a mouse tyrosinase enhancer increased leakiness of a tyrosinase promoter, although it was not affected by a human tyrosinase enhancer. Furthermore, leakiness of ttsP's was enhanced by 5'-terminal adenoviral E1A enhancers, and adenoviral E1A-13S was found to be a strong transactivator of ttsP's, leading to "autoactivation" of leaky ttsP-RRCAs. In a proof-of-principle study, ttsP-RRCA replication was shown to be inhibited by a tetracycline-controlled transcriptional silencer via direct ttsP silencing. This opens up the prospect of pharmacological regulation of ttsP-RRCAs. Together, these data indicate that leakiness of ttsP's induced by several factors is a major cause of nonspecific ttsP-RRCA replication. Consideration of these factors may help optimize ttsP-dependent RRCA vectors and may thereby improve their safety.
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PMID:Viral and nonviral factors causing nonspecific replication of tumor- and tissue-specific promoter-dependent oncolytic adenoviruses. 1577 59