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Oligomerisation of the developmental regulator proline rich homeodomain (PRH/Hex) is mediated by a novel proline-rich dimerisation domain.

TitleOligomerisation of the developmental regulator proline rich homeodomain (PRH/Hex) is mediated by a novel proline-rich dimerisation domain.
Publication TypeJournal Article
Year of Publication2006
AuthorsSoufi A, Smith C, Clarke AR, Gaston K, Jayaraman P-S
JournalJ Mol Biol
Date Published2006 May 12
KeywordsAmino Acid Sequence, Animals, Base Sequence, Cell Line, Cell Nucleus, Cercopithecus aethiops, Chemistry, Physical, COS Cells, Dimerization, DNA, Homeodomain Proteins, Humans, K562 Cells, Microscopy, Electron, Models, Molecular, Molecular Sequence Data, Physicochemical Phenomena, Proline, Protein Structure, Quaternary, Protein Structure, Tertiary, Recombinant Proteins, Solutions, Transcription Factors, Transcription, Genetic

Homeodomain proteins regulate multiple developmental pathways by altering gene expression temporally and in a tissue-specific fashion. The Proline Rich Homeodomain protein (PRH/Hex) is a transcription factor and an essential regulator of embryonic development and haematopoiesis. Recent discoveries have implicated self-association as an important feature of transcription factor function. Here, we show using a variety of techniques including gel-filtration, analytical ultracentrifugation, electron microscopy and in vitro cross-linking, that purified recombinant PRH is oligomeric and we use in vivo cross-linking to confirm that this protein exists as oligomers in cells. This is the first demonstration that a homeodomain protein can oligomerise in vivo. Consistent with these findings we show that a fraction of endogenous and exogenous PRH appears as discrete foci within the nucleus and at the nuclear periphery. The N-terminal domain of PRH is involved in the regulation of cell proliferation and transcriptional repression and can make multiple protein-protein interactions. We show that this region of PRH contains a novel proline-rich dimerisation domain that mediates oligomerisation. We propose a model that explains how PRH forms oligomers and we discuss how these oligomers might control transcription.

Alternate JournalJ. Mol. Biol.
PubMed ID16540119
Grant ListBB/D005094/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
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