The Ovarian Carcinoma Immunoreactive Antigen domain (OCIAD) - containing proteins OCIAD1/Asrij and OCIAD2, are implicated in several cancers and neurodegenerative diseases. While Asrij has a conserved role in facilitating STAT3 activation for JAK/STAT signaling, the expression and function of OCIAD2 in non-cancerous contexts remains unknown. Here, we report that ociad2 neighbors ociad1/asrij in most vertebrate genomes, and the two genes likely arose by tandem gene duplication, probably somewhere between the Ordovician and Silurian eras. We show that ociad2 expression is higher in the mouse kidney, liver and brain relative to other tissues. OCIAD2 localizes to early endosomes and mitochondria, and interacts with Asrij and STAT3. Knockdown and overexpression studies showed that OCIAD2 is essential for STAT3 activation and cell migration, which could contribute to its role in tumor metastasis. Structure prediction programs, protein disruption studies, biochemical and functional assays revealed a double helical motif in the OCIA domain that is necessary and sufficient for its localization, interactions and STAT3 activation. Given the importance of JAK/STAT signaling in development and disease, our studies shed light on the evolution and conserved function of the OCIA domain in regulating this pathway and will be critical for understanding this clinically important protein family.
Link to full article: https://www.nature.com/articles/s41598-018-25667-3
Comparison of the genomic organization for ociad1 and ociad2 across different species. Schematics depict genomic region encompassing ociad1 (red) and ociad2 (blue) and flanking genes fryl, cwh43 or dcun1d4 as indicated. Chromosome numbers and position of genes on sense or antisense strand are indicated. Direction of arrows indicates direction of transcription. Phyla are grouped into colored boxes.
Proposed model depicting the location of OCIAD1 and OCIAD2 and their interaction via the double helical motif (wavy grey lines). Blue shading: conserved region; Yellow: non-conserved regions. STAT3 interaction with OCIAD1 or OCIAD2 (individually or together) leads to STAT3 activation essential for cell migration.
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