PRH/Hex: an oligomeric transcription factor and multifunctional regulator of cell fate

Abstract

The PRH (proline-rich homeodomain) [also known as Hex (haematopoietically expressed homeobox)] protein is a critical regulator of vertebrate development. PRH is able to regulate cell proliferation and differentiation and is required for the formation of the vertebrate body axis, the haematopoietic and vascular systems and the formation of many vital organs. PRH is a DNA-binding protein that can repress and activate the transcription of its target genes using multiple mechanisms. In addition, PRH can regulate the nuclear transport of specific mRNAs making PRH a member of a select group of proteins that control gene expression at the transcriptional and translational levels. Recent biophysical analysis of the PRH protein has shown that it forms homo-oligomeric complexes in vivo and in vitro and that the proline-rich region of PRH forms a novel dimerization interface. Here we will review the current literature on PRH and discuss the complex web of interactions centred on this multifunctional protein.

PRH/HHex inhibits the migration of breast and prostate epithelial cells through direct transcriptional regulation of Endoglin

“…However, at other promoters PRH binds in conjunction with other transcription factors and in these cases extensive direct contacts between PRH and the DNA may not be required (1). Surprisingly, although the promoter proximal binding sites in the Endoglin promoter confer responsiveness to PRH over-expression in luciferase assays, PRH appears to repress Endoglin transcription when bound at these sites.…”

“…The transcription factor PRH (Proline Rich Homeodomain/HHex) is essential for formation of the vertebrate body axis and the development of most organs including the heart, thyroid, pancreas, vasculature and haematopoietic compartment (1). PRH can activate or repress transcription of its target genes and it can also control gene expression at the posttranscriptional level via a protein-protein interaction with eIF4E (2)(3)(4)(5).…”

Homeoprotein hhex-induced conversion of intestinal to ventral pancreatic precursors results in the formation of giant pancreata in Xenopus embryos

“…1A, [5][6][7][8][9][10][11][12]. In consequence, during neurulation (stage [14][15][16][17][18][19][20][21][22], two separate cell populations can be distinguished in the anterior ventral foregut endoderm: a more anterio-dorsal domain expressing hhex and a directly adjacent postero-ventral group of cells expressing vpp1 (Fig. 1A, 13-16).…”

“…The homeodomain transcription factor Hhex serves key regulatory functions both in the context of liver and ventral pancreas development (17). In Hhex-null mouse embryos, the hepatic diverticulum is normally specified within the early ventral foregut endoderm (18,19); however, proliferation of these cells in the liver diverticulum is inhibited, leading to morphogenetic and movement defects.…”

Overexpression of Hematopoietically Expressed Homeoprotein Induces Nonapoptotic Cell Death in Mouse Prechondrogenic ATDC5 Cells

“…[12][13][14][15][16][17] In hematopoiesis, Hex is required for the differentiation of hemangioblasts into hematopoietic progenitors and the repression of hemangioblast proliferation. 18,19) Hex is essential for normal liver morphogenesis by promoting the differentiation of hepatic endoderm into hepatoblasts through the transition to a pseudostratified epithelium, and by the activation of several liver-specific genes such as hepatocyte nuclear factors.…”