The Function of PML in p53-dependent Apoptosis

Nat Cell Biol. 2000 Oct;2(10):730-6. doi: 10.1038/35036365.

Abstract

The PML gene of acute promyelocytic leukaemia (APL) encodes a growth- and tumour-suppresor protein that is essential for several apoptotic signals. The mechanisms by which PML exerts its pro-apoptotic function are still unknown. Here we show that PML acts as a transcriptional co-activator with p53. PML physically interacts with p53 both in vitro and in vivo and co-localizes with p53 in the PML nuclear body (PML-NB). The co-activatory role of PML depends on its ability to localize in the PML-NB. p53-dependent, DNA-damage-induced apoptosis, transcriptional activation by p53, the DNA-binding ability of p53, and the induction of p53 target genes such as Bax and p21 upon gamma-irradiation are all impaired in PML-/- primary cells. These results define a new PML-dependent, p53-regulatory pathway for apoptosis and shed new light on the function of PML in tumour suppression.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Compartmentation
  • Cell Nucleus / ultrastructure
  • DNA Damage
  • Gamma Rays
  • Gene Expression Regulation, Neoplastic*
  • Leukemia, Promyelocytic, Acute / genetics*
  • Mice
  • Mice, Mutant Strains
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Nuclear Proteins*
  • Promyelocytic Leukemia Protein
  • Signal Transduction
  • Thymus Gland / cytology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins

Substances

  • Neoplasm Proteins
  • Nuclear Proteins
  • Pml protein, mouse
  • Promyelocytic Leukemia Protein
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins