title: BID regulation by p53 contributes to chemosensitivity.
abstract: The role of the p53 protein (encoded by TP53) in tumour suppression relies partly on the ability of p53 to regulate the transcription of genes that are important in cell-cycle arrest and in apoptosis. But the apoptotic pathway mediated by p53 is not fully understood. Here we show that BID, a member of the pro-apoptotic Bcl-2 family of proteins, is regulated by p53. BID mRNA is increased in a p53-dependent manner in vitro and in vivo, with strong expression in the splenic red pulp and colonic epithelium of gamma-irradiated mice. Both the human and the mouse BID genomic loci contain p53-binding DNA response elements that bind p53 and mediate p53-dependent transactivation of a reporter gene. In addition, BID-null mouse embryonic fibroblasts are more resistant than are wild-type fibroblasts to the DNA damaging agent adriamycin and the nucleotide analogue 5-fluorouracil, both of which stabilize endogenous p53. Our results indicate that BID is a p53-responsive 'chemosensitivity gene' that may enhance the cell death response to chemotherapy.
authors.affiliation: Laboratory of Molecular Oncology and Cell Cycle Regulation, Howard Hughes Medical Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Joanna K
authors.initials: JK
authors.lastname: Sax
authors.forename: Peiwen
authors.initials: P
authors.lastname: Fei
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Murphy
authors.forename: Eric
authors.initials: E
authors.lastname: Bernhard
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Korsmeyer
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis / Q000502:physiology*; D016923:Cell Death; D002460:Cell Line; D002469:Cell Separation; D002843:Chromatin / Q000378:metabolism; D003106:Colon / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology; D004249:DNA Damage; D018076:DNA, Complementary / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology; D005720:Gamma Rays; D005786:Gene Expression Regulation; D006801:Humans; D017403:In Situ Hybridization; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011487:Protein Conformation; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013696:Temperature; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D017304:Annexin A5; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C494815:Bid protein, mouse; D002352:Carrier Proteins; D002843:Chromatin; D004396:Coloring Agents; D018076:DNA, Complementary; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D008156:Luciferases; D005472:Fluorouracil