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Genes & Dev. 18 (15): 1812-1823

Copyright © 2004 by Cold Spring Harbor Laboratory Press.

RESEARCH PAPER

Regulation of multimers via truncated isoforms: a novel mechanism to control nitric-oxide signaling

Yuri Stasiv, Boris Kuzin, Michael Regulski, Tim Tully, and Grigori Enikolopov1

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA

Abstract: 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.

Key Words: Nitric oxide • Drosophila • development • signaling • imaginal disc

Received for publication January 25, 2004. Accepted for publication June 1, 2004.

Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.298004.

1 Corresponding author. E-MAIL enik{at}cshl.edu; FAX (516) 367-6805.

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