Molecular characterization of the tumor-associated antigen AAA-TOB3

Abstract.

In search for new valuable tumor-associated antigens using the AMIDA technique, we identified the KIAA 1273-AAA-TOB3 protein. KIAA 1273 and AAA-TOB3 were considered synonyms for the atad3B gene product. We show that the atad3b gene encodes two distinct proteins, both overexpressed in head and neck carcinomas and required for correct cell division. Both products differ within the N terminus, are generated upon distinct transcription initiation sites, and have been termed AAA-TOB3_s and AAA-TOB3_l. Both isoforms are early targets of c-myc and are located in mitochondria. A previous report suggested pro-apoptotic properties of the murine homolog of AAA-TOB3_l. Here, we did not observe any pro-apoptotic effects in human cell lines, overexpressing h-AAA-TOB3_s or h-AAA-TOB3_l. By contrast, the specific knock-down of both mRNAs resulted in polynuclear cells and decreased proliferation, along with dysfunctional cell division followed by increased apoptosis. Thus, the present data suggest a role for AAA-TOB3_s/l in tumor progression.