title: Molecular dissection of the architectural transcription factor HMGA2.
abstract: HMGA2 protein belongs to the High Mobility Group A (HMGA) family of architectural transcription factors. These proteins establish a network of protein-protein and protein-DNA interactions resulting in the formation of enhanceosomes at promoters and enhancers regulating the expression of several genes. HMGA2 dysregulation, as a result of specific chromosomal rearrangements, has been identified in a variety of common benign mesenchymal tumors, and transgenic mice expressing a truncated form of HMGA2 protein demonstrated a causal relationship between the expression of the HMGA2 protein and tumorigenesis. In this paper, using several recombinant mutant proteins, we have investigated the role played by the different domains of HMGA2 in protein-protein and protein-DNA interaction. Using the IFN-beta gene as a model, we have shown that a short region of HMGA2, comprising the second DNA-binding domain, is critical for enhancing the NF-kappaB complex formation, for binding to the PRDII element, and also for protein-protein interaction with the NF-kappaB p50 subunit. Moreover, we have analyzed the interaction of HMGA2 mutant proteins with different DNA targets demonstrating that the absence of the C-terminal tail alters HMGA2/DNA complexes in a subset of DNA sequences. Our results suggest possible implications for the role of HMGA2 in tumorigenesis.
authors.affiliation: Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, University of Trieste, via L. Giorgieri 1, Trieste, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Noro
authors.forename: Barbara
authors.initials: B
authors.lastname: Licheri
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sgarra
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rustighi
authors.forename: Michela A
authors.initials: MA
authors.lastname: Tessari
authors.forename: Kai-Yin
authors.initials: KY
authors.lastname: Chau
authors.forename: Santa Jeremy
authors.initials: SJ
authors.lastname: Ono
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Giancotti
authors.forename: Guidalberto
authors.initials: G
authors.lastname: Manfioletti
mesh_terms: D004247:DNA / Q000378:metabolism*; D025743:HMGA2 Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D025743:HMGA2 Protein; D016328:NF-kappa B; D014157:Transcription Factors; D004247:DNA