Multi-functional gene ASY/Nogo/RTN-X/RTN4: apoptosis, tumor suppression, and inhibition of neuronal regeneration.

Abstract

ASY, also designated Nogo, RTN-X, or RTN4, is a reticulon family protein containing two transmembrane domains and a C-terminal double lysine endoplasmic reticulum (ER) retrieval motif. Three protein variants are synthesized from the cognate mRNAs produced by alternative splicing, and are expressed in almost all tissues, localizing predominantly in the ER. The ASY protein induces apoptosis in various cancer cells when overexpressed, whereas normal cells are relatively resistant to ASY-dependent apoptosis. Furthermore, transcription of this gene is suppressed in certain types of cancers, suggesting that ASY may act to suppress tumor development. Although the physiological function of this protein has not been well defined, Nogo-A protein, the large variant of ASY, has been shown to inhibit neuronal regeneration in the central nervous system. Therefore, the products of this gene may be multi-functional, regulating apoptosis, tumor development, and neuronal regeneration.