The function of PML in p53-dependent apoptosis

Ailan Guo, Paolo Salomoni, Jianyuan Luo, Alan Shih, Sue Zhong, Wei Gu, Pier Paolo Pandolfi

Research output: Contribution to journalArticlepeer-review

400 Scopus citations

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 γ-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.

Original languageEnglish
Pages (from-to)730-736
Number of pages7
JournalNature Cell Biology
Volume2
Issue number10
DOIs
StatePublished - Oct 2000
Externally publishedYes

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