title: The Pbx interaction motif of Hoxa1 is essential for its oncogenic activity.
abstract: Hoxa1 belongs to the Hox family of homeodomain transcription factors involved in patterning embryonic territories and governing organogenetic processes. In addition to its developmental functions, Hoxa1 has been shown to be an oncogene and to be overexpressed in the mammary gland in response to a deregulation of the autocrine growth hormone. It has therefore been suggested that Hoxa1 plays a pivotal role in the process linking autocrine growth hormone misregulation and mammary carcinogenesis. Like most Hox proteins, Hoxa1 can interact with Pbx proteins. This interaction relies on a Hox hexapeptidic sequence centred on conserved Tryptophan and Methionine residues. To address the importance of the Hox-Pbx interaction for the oncogenic activity of Hoxa1, we characterized here the properties of a Hoxa1 variant with substituted residues in the hexapeptide and demonstrate that the Hoxa1 mutant lost its ability to stimulate cell proliferation, anchorage-independent cell growth, and loss of contact inhibition. Therefore, the hexapeptide motif of Hoxa1 is required to confer its oncogenic activity, supporting the view that this activity relies on the ability of Hoxa1 to interact with Pbx.
authors.affiliation: Molecular and Cellular Animal Embryology Group, Life Sciences Institute (ISV), Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Delval
authors.forename: Arnaud
authors.initials: A
authors.lastname: Taminiau
authors.forename: Juliette
authors.initials: J
authors.lastname: Lamy
authors.forename: Cécile
authors.initials: C
authors.lastname: Lallemand
authors.forename: Christine
authors.initials: C
authors.lastname: Gilles
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.forename: René
authors.initials: R
authors.lastname: Rezsohazy
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003260:Contact Inhibition / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000378:metabolism; D009857:Oncogenes; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000099261:Homeobox A1 Protein
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009842:Oligopeptides; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D000099261:Homeobox A1 Protein; C083400:PBX1 protein, human