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

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Oligomerisation of the developmental regulator proline rich homeodomain (PRH/Hex) is mediated by a novel proline-rich dimerisation domain. / Soufi, Abdenour; Smith, C; Clarke, AR; Gaston, Kevin; Jayaraman, Padma-Sheela.

In: Journal of Molecular Biology, Vol. 358, No. 4, 12.05.2006, p. 943-62.

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@article{9ac7f3b80f2c4fd0a0ecebd59a99780f,
title = "Oligomerisation of the developmental regulator proline rich homeodomain (PRH/Hex) is mediated by a novel proline-rich dimerisation domain",
abstract = "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.",
author = "Abdenour Soufi and C Smith and AR Clarke and Kevin Gaston and Padma-Sheela Jayaraman",
year = "2006",
month = may,
day = "12",
doi = "10.1016/j.jmb.2006.02.020",
language = "English",
volume = "358",
pages = "943--62",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - Oligomerisation of the developmental regulator proline rich homeodomain (PRH/Hex) is mediated by a novel proline-rich dimerisation domain

AU - Soufi, Abdenour

AU - Smith, C

AU - Clarke, AR

AU - Gaston, Kevin

AU - Jayaraman, Padma-Sheela

PY - 2006/5/12

Y1 - 2006/5/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33646114759&partnerID=8YFLogxK

U2 - 10.1016/j.jmb.2006.02.020

DO - 10.1016/j.jmb.2006.02.020

M3 - Article

C2 - 16540119

VL - 358

SP - 943

EP - 962

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 4

ER -