PAX5 (paired box gene 5)

9p13.2

391 amino acids; from N-term to C-term, PAX5 contains: a paired domain (aa: 16-142); an octapeptide (aa: 179-186); a partial homeodomain (aa: 228-254); a transactivation domain (aa: 304-359); and an inhibitory domain (aa: 359-391). Lineage-specific transcription factor; recognizes the concensus recognition sequence GNCCANTGAAGCGTGAC, where N is any nucleotide. Involved in B-cell differentiation. Entry of common lymphoid progenitors into the B cell lineage depends on E2A, EBF1, and PAX5; activates B-cell specific genes and repress genes involved in other lineage commitments. Activates the surface cell receptor CD19 and repress FLT3. Pax5 physically interacts with the RAG1/RAG2 complex, and removes the inhibitory signal of the lysine-9-methylated histone H3, and induces V-to-DJ rearrangements. Genes repressed by PAX5 expression in early B cells are restored in their function in mature B cells and plasma cells, and PAX5 repressed (Fuxa et al., 2004; Johnson et al., 2004; Zhang et al., 2006; Cobaleda et al., 2007; Medvedovic et al., 2011).

PML (promyelocytic leukemia)

15q24.1

882 amino-acids (aa) and shorter isoforms with distinct C terminus sequences; from N-term to C-term, PML contains: a proline rich domain (aa 3-46); a zinc finger (RING finger type) (aa 57-92); two zinc fingers (B-box types) (aa 124-166 and aa 183-236); a coiled coil made of hydrophobic aa heptad repeats (aa 228-253); an interaction domain with PER2 (aa 448-555); a nuclear localization signal (aa 476-490); a proline rich domain (aa 504-583); a serine rich domain (aa 506-540); and a sumo interaction motif (aa 556-562). The RING finger, B-boxes, and coiled-coil region form a tripartite motif known as the TRIM or the RBCC motif, and is associated with E3 ubiquitin ligase activity. PML is the organizer of nuclear domains called nuclear bodies, which recruit a wide variety of proteins, most often sumoylated. PML is involved in DNA damage response, cell division control, chromosome instability, and is a clock regulator via regulation of PER2 expression. PML has pro-apoptotic functions, induces senescence, inhibits angiogenesis and cell migration (Grignani et al., 1996; Chen et al., 2012; de Thé et al., 2012).