The function of PML in p53-dependent apoptosis Academic Article uri icon

Overview

MeSH Major

  • Apoptosis
  • Gene Expression Regulation, Neoplastic
  • Leukemia, Promyelocytic, Acute
  • Neoplasm Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Tumor Suppressor Protein p53

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 date

  • October 2000

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1038/35036365

PubMed ID

  • 11025664

Additional Document Info

start page

  • 730

end page

  • 6

volume

  • 2

number

  • 10