The Drosophila nitric-oxide synthase gene (dNOS) encodes a family of proteins that can modulate NOS activity by acting as dominant negative regulators

Stasiv, Y., Regulski, M., Kuzin, B., Tully, T., Enikolopov, G. (November 2001) The Drosophila nitric-oxide synthase gene (dNOS) encodes a family of proteins that can modulate NOS activity by acting as dominant negative regulators. Journal of Biological Chemistry, 276 (45). pp. 42241-42251. ISSN 0021-9258

URL: http://www.ncbi.nlm.nih.gov/pubmed/11526108
DOI: 10.1074/jbc.M105066200

Abstract

Nitric oxide (NO) is involved in organ development, synaptogenesis, and response to hypoxia in Drosophila. We cloned and analyzed the only gene in the fly genome that encodes Drosophila nitric-oxide synthase (dNOS). It consists of 19 exons and is dispersed over 34 kilobases of genomic DNA. Alternative transcription start sites and alternative splice sites are used to generate a remarkable variety of mRNAs from the dNOS gene. We identified eight new transcripts that are widely expressed throughout Drosophila development and encode a family of DNOS-related proteins. Alternative splicing affects both the 5'-untranslated region and the coding region of the dNOS primary transcript. Most of the splicing alterations in the coding region of the gene lead to premature termination of the open reading frame. As a result, none of the alternative transcripts encode an enzymatically active protein. However, some of these shorter DNOS protein products can effectively inhibit enzymatic activity of the full-length DNOS1 protein when co-expressed in mammalian cells, thus acting as dominant negative regulators of NO synthesis. Using immunoprecipitation, we demonstrate that these short DNOS protein isoforms can form heterodimers with DNOS1, pointing to a physical basis for the dominant negative effect. Our results suggest a novel regulatory function for the family of proteins encoded by the Drosophila NOS gene.

Item Type: Paper
Uncontrolled Keywords: MESSENGER-RNA EXPRESSION DIVERSITY PATHWAY HEME
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > small molecules > nitric oxide
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > nitric oxide synthase
CSHL Authors:
Communities: CSHL labs > Enikopolov lab
CSHL labs > Tully lab
Depositing User: Matt Covey
Date: November 2001
Date Deposited: 20 Dec 2013 16:31
Last Modified: 20 Dec 2013 16:31
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29131

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