Regulation of multimers via truncated isoforms: a novel mechanism to control nitric-oxide signaling.
Nitric oxide (NO) is an essential regulator of Drosophila development and physiology. We describe a novel mode of regulation of NO synthase (NOS) function that uses endogenously produced truncated protein isoforms of Drosophila NOS (DNOS). These isoforms inhibit NOS enzymatic activity in vitro and in vivo, reflecting their ability to form complexes with the full-length DNOS protein (DNOS1). Truncated isoforms suppress the antiproliferative action of DNOS1 in the eye imaginal disc by impacting the retinoblastoma-dependent pathway, yielding hyperproliferative phenotypes in pupae and adult flies. Our results indicate that endogenous products of the dNOS locus act as dominant negative regulators of NOS activity during Drosophila development.
Stasiv
Yuri
Y
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Kuzin
Boris
B
Regulski
Michael
M
Tully
Tim
T
Enikolopov
Grigori
G
D017398:Alternative Splicing; D000818:Animals; D030801:Animals, Genetically Modified; D001973:Bromodeoxyuridine; D002455:Cell Division; D002478:Cells, Cultured; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005123:Eye / Q000187:drug effects / Q000254:growth & development*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D020033:Protein Isoforms; D011679:Pupa / Q000254:growth & development; D016160:Retinoblastoma Protein / Q000378:metabolism; D016196:S Phase; D015398:Signal Transduction / Q000187:drug effects
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D020033:Protein Isoforms; D016160:Retinoblastoma Protein; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001973:Bromodeoxyuridine