NFX1, Its Isoforms and Roles in Biology, Disease and Cancer

SIMPLE SUMMARY: The NFX1 gene, and its gene products, were identified over 30 years ago. Since then, the literature on NFX1 homologs and NFX1 itself has grown. In this review, we summarize the studies to-date on the NFX1 gene and its proteins across species and in humans, describing their role in gene regulation, embryonic development, cellular growth and differentiation, exogenous stress tolerance and metabolism, and an organism’s immune response. We also highlight the roles NFX1 has in human disease and in cancer, with a strong focus on its collaborative role with high-risk human papillomavirus infections that cause cervical and head and neck cancers. We believe this is the first comprehensive review of NFX1 and its functional significance in organisms ranging from yeast to human. ABSTRACT: In 1989, two NFX1 protein products were identified as nuclear proteins with the ability to bind to X-box cis-elements. Since that publication, the NFX1 gene and its homologs have been identified, from yeast to humans. This review article summarizes what is known about the NFX1 gene across species. We describe the gene and protein motifs of NFX1 homologs and their functions in cellular biology, then turn to NFX1 in human biology and disease development. In that, we focus on more recent literature about NFX1 and its two splice variants protein products (NFX1-91 and NFX1-123) that are expressed in epithelial cells. We describe new evidence of conserved protein motifs, direct and indirect gene expression regulation, and critical protein-protein interactions. Finally, we stress the emerging roles of these NFX1 splice variants in high-risk human papillomavirus-associated cancers, and the increased expression of the longer splice variant, NFX1-123, found in these cancers.