Novel alternative PBX3 isoforms in leukemia cells with distinct interaction specificities

PBX3 is a member of the PBX family of TALE homeobox genes. The prototypic m ember, PBX1, was first identified in chromosomal translocations in B-lineag e leukemia and is required for normal hematopoiesis. PBX2 and PBX3 were lat er identified as members of this highly conserved family by their strong ho mology to PBX1. While the expression pattern of PBX1 is restricted, PBX2 an d PBX3 are ubiquitously expressed. Little is known about the functional rol e of PBX3. Our studies identified two PBX3 transcripts alternative to the c anonical forms, PBX3A and PBX3B, resulting from a novel splice in PBX3. The se new isoforms, named PBX3C and PBX3D, have been detected in all tissues a nd cell lines tested. Intriguingly, expression of PBX3D is favored in norma l cells, whereas PBX3C expression is favored in leukemia cells. Functional studies showed that PBX3C and PBX3D proteins were unable to interact with t he PBX-interacting factor PREP 1 and weakly interacted with MEIS proteins. We propose that PBX3C and PBX3D may affect PBX3-mediated transcriptional re gulation by acting in opposition to the known PBX proteins through alternat ive PBX3 complex formation. The identification and characterization of thes e novel PBX3 isoforms provide a foundation for a better understanding of th e biological role of PBX3. (C) 2001 Wiley-Liss, Inc.