HHex (human hematopoietically expressed homeobox) originally identified as PRH (Proline-Rich Homeodomain) protein^[1], also known in mouse as Hex protein. PRH is an essential regulator of vertebrate development and is required for the formation of the vertebrate body axis as well as the formation of haematopoietic and vascular systems. PRH also plays essential roles in the formation of vital organs including liver, thyroid, heart and pancreas. Expression of PRH is developmentally controlled through many signaling pathways. In the haematopoietic compartment it is influenced by the relative levels of Myb, GATA-1, GATA-2, SP1 and SP3 transcription factors^[2].

PRH is a potent regulator of cell proliferation and loss of nuclear PRH, and/or loss of functional PRH is associated with a subset of acute myeloid leukaemia (AML) and chronic myeloid leukaemias (CML) as well as with thyroid and breast cancers^[3][4][5]. Expression of a fusion protein between the nucleoporin protein Nup98 and PRH has also resulted in the formation of a myeloid leukaemia^[6]. In this case the fusion protein is suggested to antagonize the function of the wild type PRH protein.

PRH is a DNA binding transcription factor that can both repress and activate transcription of its target genes but is has been most extensively characterized as a repressor protein^[2]. PRH can regulate transcription directly by binding to DNA sequences or more indirectly by modulating the activity of other transcription factors through protein-protein interactions. PRH is a homo-oligomer in vivo and in vitro and binds co-operatively to promoters containing multiple PRH binding sites that are closely clustered^[7][8]. The Proline-Rich N-terminal domain provides a platform for other proteins to bind to PRH, including members of the TLE family of known co-repressors, PML, protein kinase CK2 and the C8 subunit of the proteasome^{[9][10][11][12]}. TLE proteins are also oligomeric and can recruit histone deacetylases, to compact chromatin and form repressive chromatin domains. PRH is also able to repress gene expression post-transcriptionally through a protein-protein interaction with eIF4E which down regulates the transport of specific mRNA by eIF4E^[3].