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

1. Yuri Stasiv,
2. Boris Kuzin,
3. Michael Regulski,
4. Tim Tully, and
5. Grigori Enikolopov1
6. 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.

• Nitric oxide
• Drosophila
• development
• signaling
• imaginal disc

Footnotes

• 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.

• • Accepted June 1, 2004.
  • Received January 25, 2004.

• Cold Spring Harbor Laboratory Press

•