RB18A, whose gene is localized on chromosome 17q12-q21.1, regulates in vivo p53 transactivating activity.
Among the different cellular factors that regulated p53 functions, we previously identified (P. Drane et al., Oncogene, 15: 3013-3024, 1997) RB18A, a new gene whose encoded Mr 205,000 protein interacted in vitro, through its COOH-terminal domain, with p53. Therefore, we analyzed the in vivo role of RB18A by measuring its effect on the transactivating activity of p53 on physiological promoters. We herein demonstrated that RB18A, which interacted also in vivo with p53, activated Bax promoter and inhibited p21Waf1 or IGF-BP3 promoters. In addition, fluorescence in situ hybridization mapping led to localizing the RB18A gene on chromosome 17q12-q21.1, loci associated with human cancers. This is the first demonstration that in vivo RB18A, in a protein-protein interaction, regulates p53 transactivating activity.
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Immunochimie des Régulations Cellulaires et des Interactions Virales, Institut National de la Santé et de la Recherche Médicale (INSERM) U.354, Centre INSERM, H pital Saint-Antoine, Paris, France. frade354@easynet.fr
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D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002886:Chromosomes, Human, Pair 17; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D020014:K562 Cells / Q000378:metabolism / Q000502:physiology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D056913:Mediator Complex Subunit 1; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C493956:CDKN1A protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018972:Insulin-Like Growth Factor Binding Protein 3; C538855:MED1 protein, human; D056913:Mediator Complex Subunit 1; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein