A Newly Characterized, Two BRCT Domain-Containing Isoform of PAX-Interacting Protein (PTIP) Generated via Frame Shift and Alternative Pre-mRNA Splicing

In an effort to clone polyglutamine-rich factors from activated B lymphocytes of mice, we discovered and describe here a previously uncharacterized isoform of PTIP/PAXIP1. By virtue of a two-nucleotide frameshift followed by alternative pre-mRNA splicing, this shorter isoform of 576 amino acids (termed PTIP576) retained only the two central BRCT domains of previously characterized PTIP and encodes a unique and structurally disordered 50 residue C-terminus. PTIP576 is expressed primarily in nuclei of progenitor and activated mature B lymphocytes. Transgenic overexpression of PTIP576 in murine B and T cells led to increased lineages of bone marrow B cells and thymocyte CD4 T cells. We conclude by addressing potential functions of PTIP576 resulting from the relatively unique mechanism by which it is engendered.