BID regulation by p53 contributes to chemosensitivity

Nat Cell Biol. 2002 Nov;4(11):842-9. doi: 10.1038/ncb866.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Annexin A5 / pharmacology
  • Apoptosis
  • BH3 Interacting Domain Death Agonist Protein
  • Blotting, Northern
  • Blotting, Western
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / physiology*
  • Cell Death
  • Cell Line
  • Cell Separation
  • Chromatin / metabolism
  • Colon / metabolism
  • Coloring Agents / pharmacology
  • DNA Damage
  • DNA, Complementary / metabolism
  • Doxorubicin / pharmacology
  • Epithelium / metabolism
  • Female
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Fluorouracil / pharmacology
  • Gamma Rays
  • Gene Expression Regulation*
  • Humans
  • In Situ Hybridization
  • Luciferases / metabolism
  • Mice
  • Models, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Plasmids / metabolism
  • Precipitin Tests
  • Protein Conformation
  • RNA, Messenger / metabolism
  • Spleen / metabolism
  • Temperature
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / physiology*


  • Annexin A5
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Bid protein, mouse
  • Carrier Proteins
  • Chromatin
  • Coloring Agents
  • DNA, Complementary
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • Doxorubicin
  • Luciferases
  • Fluorouracil