title: Insights into specificity, redundancy and new cellular functions of C/EBPa and C/EBPb transcription factors through interactome network analysis.
abstract: C/EBPa and C/EBPb are transcription factors with tissue specific expression regulating several important cellular processes. They work by recruiting protein complexes to a common DNA recognition motif and both are able to compensate each other's absence in many cell types, thus showing functional redundancy. They also play distinct roles in specific cellular pathways and their abnormal functioning gives raise to different human pathologies.
  
  
  
  To investigate the molecular basis of C/EBPa and C/EBPb specificity and redundancy we characterized their in vivo protein-protein interaction networks by Tandem Affinity Purification (TAP) and Mass Spectrometry (MS). To unravel the functional features of C/EBPa and C/EBPb proteomes we studied the statistical enrichment of binding partners related to Gene Ontology (GO) terms and KEGG pathways.
  
  
  
  Our data confirmed that the C/EBPa and C/EBPb regulate biological processes like cell proliferation, apoptosis and transformation. We found that both C/EBPa and C/EBPb are involved in other cellular pathways such as RNA maturation, RNA splicing and DNA repair. Specific interactions of C/EBPa with MRE11, RUVBL1 and RUVBL2 components of DNA repair system were confirmed by co-immunoprecipitation assays.
  
  
  
  Our comparative analysis of the C/EBPa and C/EBPb proteomes provides an insight for understanding both their redundant and specific roles in cells indicating their involvement in new pathways. Such novel predicted functions are relevant to normal cellular processes and disease phenotypes controlled by these transcription factors.
  
  
  
  Functional characterization of C/EBPa and C/EBPb proteomes suggests they can regulate novel pathways and indicate potential molecular targets for therapeutic intervention.
authors.affiliation: Institute of Cell Biology and Neurobiology (IBCN), CNR, via Ramarini 32, 00015 Monterotondo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cirilli
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory, via Ramarini 32, 00015 Monterotondo, Italy; Department of Medicine, University of Perugia, Perugia 06132, Italy.
authors.forename: Oxana
authors.initials: O
authors.lastname: Bereshchenko
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory, via Ramarini 32, 00015 Monterotondo, Italy. Electronic address: olga.ermakova@cnr.it.
authors.forename: Olga
authors.initials: O
authors.lastname: Ermakova
authors.affiliation: Mouse Biology Unit, European Molecular Biology Laboratory, via Ramarini 32, 00015 Monterotondo, Italy; MRC Molecular Hematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK. Electronic address: claus.nerlov@imm.ox.ac.uk.
authors.forename: Claus
authors.initials: C
authors.lastname: Nerlov
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D051379:Mice; D041681:NIH 3T3 Cells; D060066:Protein Interaction Maps / Q000235:genetics*; D020543:Proteome / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C545013:Cebpb protein, mouse; D020543:Proteome; D014157:Transcription Factors
keywords: Adipogenesis; CCAAT/enhancer binding proteins C/EBPa and C/EBPb; DNA repair protein complexes; Large scale protein-protein interactions; Network functional analysis; RNA metabolism