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 SOX9
Homo sapiens
 HIF1A
Homo sapiens
 Pax6
Mus musculus
 PAX6
Homo sapiens
 Snai2
Mus musculus
 PPARA
Homo sapiens
 Ppara
Mus musculus
 Thrb
Mus musculus
 SNAI2
Homo sapiens
 Tbr1
Mus musculus
Transcription Factor Encyclopedia  BETA
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Overview
No annotation is available in this section for this article. The content below is taken from a related TF, HHEX (Homo sapiens).

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](pmid: 20176809). 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[8][9]. 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[10][11][12][13]. 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].

References
  1. Crompton MR et al. Identification of a novel vertebrate homeobox gene expressed in haematopoietic cells. Nucleic Acids Res., 20(21):5661-7. (PMID 1360645)
  2. Soufi A and Jayaraman PS. PRH/Hex: an oligomeric transcription factor and multifunctional regulator of cell fate. Biochem. J., 412(3):399-413. (PMID 18498250)
  3. Topisirovic I et al. The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth. EMBO J., 22(3):689-703. (PMID 12554669)
  4. Puppin C et al. HEX expression and localization in normal mammary gland and breast carcinoma. BMC Cancer, 6:192. (PMID 16854221)
  5. D'Elia AV et al. Expression and localization of the homeodomain-containing protein HEX in human thyroid tumors. J. Clin. Endocrinol. Metab., 87(3):1376-83. (PMID 11889211)
  6. Jankovic D et al. Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia. Blood, 111(12):5672-82. (PMID 18388181)
  7. Noy P et al. PRH/Hhex controls cell survival through coordinate transcriptional regulation of vascular endothelial growth factor signaling. Mol. Cell. Biol., 30(9):2120-34. (PMID 20176809)
  1. Williams H et al. DNA wrapping and distortion by an oligomeric homeodomain protein. J. Mol. Biol., 383(1):10-23. (PMID 18755198)
  2. Soufi A et al. Oligomerisation of the developmental regulator proline rich homeodomain (PRH/Hex) is mediated by a novel proline-rich dimerisation domain. J. Mol. Biol., 358(4):943-62. (PMID 16540119)
  3. Swingler TE et al. The proline-rich homeodomain protein recruits members of the Groucho/Transducin-like enhancer of split protein family to co-repress transcription in hematopoietic cells. J. Biol. Chem., 279(33):34938-47. (PMID 15187083)
  4. Topcu Z et al. The promyelocytic leukemia protein PML interacts with the proline-rich homeodomain protein PRH: a RING may link hematopoiesis and growth control. Oncogene, 18(50):7091-100. (PMID 10597310)
  5. Bess KL et al. The transcriptional repressor protein PRH interacts with the proteasome. Biochem. J., 374(Pt 3):667-75. (PMID 12826010)
  6. Soufi A et al. CK2 phosphorylation of the PRH/Hex homeodomain functions as a reversible switch for DNA binding. Nucleic Acids Res. (PMID 19324893)
Figures
No annotation is available in this section for this article. The content below is taken from a related TF, HHEX (Homo sapiens).
FIGURE 1 Model of PRH regulating gene expression in response to multiple development and cell-growth cues
A single octamer of PRH is shown bound to DNA and also to multiple PRH partners allowing PRH to respond to multiple signalling pathways simultaneously or temporally. For clarity, each subunit of PRH is not shown bound to DNA or bound to every interacting partner. Figure taken from Soufi and Jayaraman 2008.
This figure is from a publication by the authors of this article. Please click here to view the publication's entry in Pubmed (PMID 18498250).