PAX genes in cell differentiation, lineage development and pathogenesis

Members of the Pax family of genes play critical roles in development and are now known to play important roles in the progress of specific cancers. Pax genes encode transcription factor proteins containing multiple DNA binding and protein-protein interaction domains. These domains allow complex interactions with both the promoters of target genes and other proteins involved in transcriptional regulation. Also, Pax transcription factors are expressed as multiple distinct isoforms, which differ in the amino acid sequence of their DNA binding and/or protein-protein interaction domains, substantially adding to the complexity and spectrum of their interactions and resultant functions. In this chapter we discuss the roles that Pax genes play in certain processes critical to development including prevention of apoptosis, cellular proliferation and migration. We discuss how these processes may be commandeered by aberrant expression of Pax genes leading to oncogenic transformation and tumorigenesis. To further elucidate the role that Pax transcription factors play in these processes, candidate down stream target genes, and interacting protein partners are examined. Pax targets include cell cycle regulators, repressors, antiapoptotic regulators, differentiation genes and cell surface proteins
involved in migration.