title: A p53-type response element in the GDF15 promoter confers high specificity for p53 activation.
abstract: GDF15 is a transcriptional target gene for p53 and its family members, p63 and p73. Its promoter region contains two p53-type response elements, RE1 and RE2, and RE2 confers p53-specific transactivation. RE2 contains several mismatches from the canonical p53 response element (RRRCWWGYYY). Two mismatches in the RRR span and T base of the RE2 core sequence in the most 3' quarter-site are critical for inhibiting the binding affinity to p63 and p73 and corresponding promoter activity. Our results strongly suggest that differential DNA-binding affinities between p53 family member proteins act, at least in part, to confer specific target gene activation.
authors.affiliation: Department of Otolaryngology, Head and Neck Cancer Research Division, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Osada
authors.forename: Hannah Lui
authors.initials: HL
authors.lastname: Park
authors.forename: Min Joo
authors.initials: MJ
authors.lastname: Park
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Liu
authors.forename: Guojun
authors.initials: G
authors.lastname: Wu
authors.forename: Barry
authors.initials: B
authors.lastname: Trink
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D055436:Growth Differentiation Factor 15; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology*; D020218:Response Elements / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D009687:Nuclear Proteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins