Regulation of Multimers Via Truncated Isoforms: a Novel Mechanism to Control Nitric-oxide Signaling

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2004 Jul 17

PMID 15256486

Citations 10

Authors

Yuri Stasiv

Boris Kuzin

Michael Regulski

Tim Tully

Grigori Enikolopov

Affiliations

Soon will be listed here.

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.

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