title: Physical interaction of tumour suppressor p53/p73 with CCAAT-binding transcription factor 2 (CTF2) and differential regulation of human high-mobility group 1 (HMG1) gene expression.
abstract: The CCAAT-binding transcription factor (CTF)/nuclear factor I (NF-I) group of cellular DNA-binding proteins recognizes the sequence GCCAAT and is implicated in eukaryotic transcription, as well as DNA replication. Molecular analysis of human CTF/NF-I cDNA clones revealed multiple mRNA species that contain alternative coding regions, apparently as a result of differential splicing. Expression and functional analysis established that individual gene products can bind to GCCAAT recognition sites and serve as both promoter-selective transcriptional activators and initiation factors for DNA replication. The interaction between CTF2 and p53/p73 was shown to modulate their ability to regulate transcription of their respective target genes. In the present paper, we report that p53 down-regulates the activity of the high mobility group 1 (HMG1) gene promoter, whereas p73alpha up-regulates the activity of this promoter. Furthermore, CTF2 transactivates p53-induced p21 promoter activity, but inhibits p73alpha-induced p21 promoter activity. Using deletion mutants, we found that the DNA-binding domains of both p53 and p73alpha are required for physical interaction with CTF2 via the regions between amino acid residues 161 and 223, and 228 and 312 respectively. CTF2 enhances the DNA-binding activity of p53 and inhibits the DNA-binding activity of p73alpha. These results provide novel information on the functional interplay between CTF2 and p53/p73 as important determinants of their function in cell proliferation, apoptosis, DNA repair and cisplatin resistance.
authors.affiliation: Department of Molecular Biology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Uramoto
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.forename: Gunji
authors.initials: G
authors.lastname: Nagatani
authors.forename: Haruki
authors.initials: H
authors.lastname: Ohmori
authors.forename: Naofumi
authors.initials: N
authors.lastname: Nagasue
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ise
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Kosei
authors.initials: K
authors.lastname: Yasumoto
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
mesh_terms: D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: D023081:CCAAT-Binding Factor; D017931:DNA Primers; D004268:DNA-Binding Proteins; D024243:HMGB1 Protein; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins