HuD, a neuronal-specific RNA-binding protein, is a potential regulator of MYCN expression in human neuroblastoma cells Conference Paper
| Authors: | Ross, R. A.; Lazarova, D. L.; Manley, G. T.; Smitt, P. S.; Spengler, B. A.; Posner, J. B.; Biedler, J. L. |
| Title: | HuD, a neuronal-specific RNA-binding protein, is a potential regulator of MYCN expression in human neuroblastoma cells |
| Conference Title: | Advances in Neuroblastoma Research - 1996 (ANR 6) |
| Abstract: | HuD is one of a family of neural antigens recognised by the sera of patients with antibody-associated paraneoplastic encephalomyelitis. Localised exclusively to neurons, these proteins are among the earliest markers of the developing nervous system. Sequence analysis suggests that HuD is an RNA- binding protein. Hu protein levels were determined for the three cell types characterising human neuroblastoma cell lines: sympathoadrenal neuroblasts (N), substrate-adherent Schwann/glial/melanoblastic precursors (s) and stem cells (I) which can give rise to both N and S cells. Western blot analysis showed similar levels of protein in three N-type cell lines; S cells have no detectable Hu protein. Northern blot analysis indicated that N cells express all three Hu genes, HuD, HuC and Hel-N1. N cells, mostly from MYCN-amplified cell lines, have consistently higher steady-state levels of MYCN mRNA than S cell counterparts. Nuclear run-on and mRNA half-life experiments revealed no differences in transcription rate or mRNA stability between N and S cells from the LA-N-1 cell line, implicating differences in post-transcriptional regulation. HuD is postulated to be instrumental in splicing/processing and/or stabilisation of mRNAs involved in cell growth and neuronal differentiation. As determined by gel-mobility shift assays, HuD fusion protein binds to the 3'UTR of human MYCN mRNA. Analysis of HuD deletion mutants has demonstrated that the first and second RNA-recognition motifs (RRMs) are required for binding. Whether HuD regulates MYCN expression and thereby influences tumour aggressiveness is of major interest. |
| Keywords: | protein expression; human cell; sequence deletion; conference paper; neoplasm proteins; nerve tissue proteins; protein binding; cell differentiation; tumor cells, cultured; childhood cancer; cell type; rna binding protein; rna-binding proteins; neuroblastoma; messenger rna; neuroblastoma cell; rna, messenger; glia cell; binding sites; schwann cell; proto-oncogene proteins c-myc; blotting, northern; hu paraneoplastic encephalomyelitis antigens; northern blotting; human neuroblastoma; humans; human; priority journal; hud; mycn regulation |
| Journal Title | European Journal of Cancer |
| Volume: | 33 |
| Issue: | 12 |
| Conference Dates: | 1996 May 22-25 |
| Conference Location: | Philadelphia, PA |
| ISBN: | 0959-8049 |
| Publisher: | Elsevier Inc. |
| Date Published: | 1997-10-01 |
| Start Page: | 2071 |
| End Page: | 2074 |
| Language: | English |
| DOI: | 10.1016/s0959-8049(97)00331-6 |
| PUBMED: | 9516855 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Conference Paper -- Export Date: 17 March 2017 -- Source: Scopus |
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