title: Transcriptional repression of the eukaryotic initiation factor 4E gene by wild type p53.
abstract: The eukaryotic initiation factor 4E (eIF4E) plays important roles in transformation and cancer progression. It is frequently overexpressed in malignant cells, one mechanism of which is through transcriptional activation by c-myc. Here, we report that high level of eIF4E expression and its tumorigenicity could be alternatively associated with defects of p53, since we found that induction of wt-p53 repressed eIF4E expression. Gene transfection of p53 inhibited eIF4E promoter activity, while inactivation of p53 either by mutation or by over-expression of MDM2 resulted in stimulation of eIF4E promoter activity. We demonstrated that p53-repression of eIF4E was regulated by c-myc. The wt-p53 can physically bind to c-myc, which inhibited binding of c-myc to eIF4E promoter and c-myc-stimulated promoter activity. These results suggest that the expression of eIF4E is reciprocally regulated by p53 and c-myc, and loss of p53-mediated control over c-myc-dependent transactivation of eIF4E may represent a novel mechanism for eIF4E-mediated neoplastic transformation and cancer progression.
authors.affiliation: Division of Pediatric Hematology/Oncology/BMT, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Ningxi
authors.initials: N
authors.lastname: Zhu
authors.forename: Lubing
authors.initials: L
authors.lastname: Gu
authors.forename: Harry W
authors.initials: HW
authors.lastname: Findley
authors.forename: Muxiang
authors.initials: M
authors.lastname: Zhou
mesh_terms: D045744:Cell Line, Tumor; D002648:Child; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53