%0 Journal Article
%T Involvement of GTA protein NC2¦Â in Neuroblastoma pathogenesis suggests that it physiologically participates in the regulation of cell proliferation
%A Cinzia Di Pietro
%A Marco Ragusa
%A Davide Barbagallo
%A Laura R Duro
%A Maria R Guglielmino
%A Alessandra Majorana
%A Veronica Giunta
%A Antonella Rapisarda
%A Elisa Tricarichi
%A Marco Miceli
%A Rosario Angelica
%A Agata Grillo
%A Barbara Banelli
%A Isabella Defferari
%A Stefano Forte
%A Alessandro Lagan¨¤
%A Camillo Bosco
%A Rosalba Giugno
%A Alfredo Pulvirenti
%A Alfredo Ferro
%A Karl H Grzeschik
%A Andrea Di Cataldo
%A Gian P Tonini
%A Massimo Romani
%A Michele Purrello
%J Molecular Cancer
%D 2008
%I BioMed Central
%R 10.1186/1476-4598-7-52
%X To verify our hypothesis, we analyzed the involvement in Neuroblastoma (NB) pathogenesis of GTA genes localized at 1p, one of NB critical regions: through RT-PCR of fifty eight NB biopsies, we demonstrated the statistically significant reduction of the mRNA for NC2¦Â (localized at 1p22.1) in 74% of samples (p = 0.0039). Transcripts from TAF13 and TAF12 (mapping at 1p13.3 and 1p35.3, respectively) were also reduced, whereas we didn't detect any quantitative alteration of the mRNAs from GTF2B and NC2¦Á (localized at 1p22-p21 and 11q13.3, respectively). We confirmed these data by comparing tumour and constitutional DNA: most NB samples with diminished levels of NC2¦Â mRNA had also genomic deletions at the corresponding locus.Our data show that NC2¦Â is specifically involved in NB pathogenesis and may be considered a new NB biomarker: accordingly, we suggest that NC2¦Â, and possibly other GTA members, are physiologically involved in the control of cell proliferation. Finally, our studies unearth complex selective mechanisms within NB cells.Transcription initiation, the most important and regulated event along the pathway connecting genotype to phenotype, is governed by the General Transcription Apparatus (GTA): GTA proteins constitute the PreInitiation Complex (PIC) and guide its assembly [1-3]. Class II PIC, larger than 2 MDa, comprises more than fifty different polypeptides, including RNA polymerase II, GTFs, Mediator [4-6]. GTF2D consists of the TATA Box ¨C Binding Protein (TBP) and TBP ¨C Associated Factors (TAFs), a group of evolutionarily conserved proteins that participate in determining the state of chromatin, contribute to promoter recognition, serve as coactivators, and post-translationally modify other GTA proteins to facilitate PIC assembly and transcription initiation [1,5]. Its DNA binding activity is regulated by positive and negative cofactors such as heterodimeric NC2 (also named Dr1/Drap 1), comprised of ¦Á- and ¦Â-type subunits [7,8]. The molecular actions of
%U http://www.molecular-cancer.com/content/7/1/52