title: ErbB3-binding protein EBP1 decreases ErbB2 levels via a transcriptional             mechanism.
abstract: Ectopic expression of EBP1, an ErbB3-interacting protein, reduces the expression             of the ErbB2 protein and mRNA. However, the mechanism of EBP1-induced decrease             in ErbB2 mRNA levels has not yet been determined. Since EBP1 affects both transcriptional             and post-transcriptional processes, we evaluated the ability of EBP1 to regulate             ErbB2 transcription and RNA stability. We discovered that while wild-type EBP1             decreased the activity of a proximal ErbB2 promoter, EBP1 mutants unable to interact             with the Sin3A transcriptional repressor inhibited activity to a lesser extent.             EBP1 also decreased the activity of distal ErbB2 promoters. Chromatin immunoprecipitation             analysis indicated that EBP1 bound both distal and proximal endogenous ErbB2 promoters             in serum-starved conditions. The ErbB3 ligand heregulin (HRG) at growth-promoting             concentrations reduced EBP1 binding to the ErbB2 promoter. Although endogenous             EBP1 bound ErbB2 mRNA, EBP1 overexpression or ablation of EBP1 protein by shRNA             failed to alter ErbB2 mRNA stability. These results suggest that the major effect             of EBP1 on ErbB2 mRNA levels is at the transcriptional level.
authors.affiliation: Greenebaum Cancer Center, University of Maryland, Baltimore,                     MD 21201, USA.
authors.forename: Arundhati
authors.initials: A
authors.lastname: Ghosh
authors.forename: Smita
authors.initials: S
authors.lastname: Awasthi
authors.forename: Anne W
authors.initials: AW
authors.lastname: Hamburger
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C101633:PA2G4 protein, human; C508053:ERBB2 protein, human