Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vitamin A metabolite, all-trans retinoic acid (atRA), plays an important role in neuronal development, including neurite outgrowth. However, the genes that lie downstream of atRA and its receptors in neuronal cells are largely unknown. By using the human neuroblastoma cell line, SH-SY5Y, we have identified an atRA-responsive gene (RAINB1: retinoic acid inducible in neuroblastoma cells) that is induced within 4 h after exposure of SH-SY5Y cells to atRA. RAINB1 mRNA is highly expressed in the nervous system (10.5- to 11-kb transcript) in both developing embryos and adults. Its expression is perturbed in developing rat embryos exposed to excess or insufficient atRA. RAINB1 is present on chromosome 11 and is spread over 38 exons, resulting in a putative ORF of 2,429 amino acids. The RAINB1 protein shows high similarity to a gene in Caenorhabditis elegans, unc-53, that is required for axonal elongation of mechanosensory neurons, suggesting that these proteins are orthologs. Thus, RAINB1 may represent a critical downstream gene in atRA-mediated neurite outgrowth.
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PMID:A mammalian homolog of unc-53 is regulated by all-trans retinoic acid in neuroblastoma cells and embryos. 1190 4

The vitamin A metabolite, all-trans retinoic acid (atRA) plays essential roles in nervous system development, including neuronal patterning, survival, and neurite outgrowth. Our understanding of how the vitamin A acid functions in neurite outgrowth comes largely from cultured embryonic neurons and model neuronal cell systems including human neuroblastoma cells. Specifically, atRA has been shown to increase neurite outgrowth from embryonic DRG, sympathetic, spinal cord, and olfactory receptor neurons, as well as dissociated cerebra and retina explants. A role for atRA in axonal elongation is also supported by a limited number of studies in vivo, in which a deficiency in retinoid signaling produced either by dietary or genetic means has been shown to alter neurite outgrowth from the spinal cord and hindbrain regions. Human neuroblastoma cells also show enhanced numbers of neurites and longer processes in response to atRA. The mechanism whereby retinoids regulate neurite outgrowth includes, but is not limited to, the regulation of the transcription of neurotrophin receptors. More recent evidence supports a role for atRA in regulating components of other signaling pathways or candidate neurite-regulating factors. Some of these effects, such as that on neuron navigator 2 (NAV2), may be direct, whereas others may be secondary to other atRA-induced changes in the cell. This review focuses on what is currently known about neurite initiation and growth, with emphasis on the manner in which atRA may influence these events.
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PMID:Role of all-trans retinoic acid in neurite outgrowth and axonal elongation. 1668 69

Neuron navigator 2 (Nav2) was first identified as an all-trans retinoic acid (atRA)-responsive gene in human neuroblastoma cells (retinoic acid-induced in neuroblastoma 1, RAINB1) that extend neurites after exposure to atRA. It is structurally related to the Caenorhabditis elegans unc-53 gene that is required for cell migration and axonal outgrowth. To gain insight into NAV2 function, the full-length human protein was expressed in C. elegans unc-53 mutants under the control of a mechanosensory neuron promoter. Transgene expression of NAV2 rescued the defects in unc-53 mutant mechanosensory neuron elongation, indicating that Nav2 is an ortholog of unc-53. Using a loss-of-function approach, we also show that Nav2 induction is essential for atRA to induce neurite outgrowth in SH-SY5Y cells. The NAV2 protein is located both in the cell body and along the length of the growing neurites of SH-SY5Y cells in a pattern that closely mimics that of neurofilament and microtubule proteins. Transfection of Nav2 deletion constructs in Cos-1 cells reveals a region of the protein (aa 837-1065) that directs localization with the microtubule cytoskeleton. Collectively, this work supports a role for NAV2 in neurite outgrowth and axonal elongation and suggests this protein may act by facilitating interactions between microtubules and other proteins such as neurofilaments that are key players in the formation and stability of growing neurites.
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PMID:The atRA-responsive gene neuron navigator 2 functions in neurite outgrowth and axonal elongation. 1872 12