The function of PML in p53-dependent apoptosis Journal Article

  


Authors: Guo, A.; Salomoni, P.; Luo, J.; Shih, A.; Zhong, S.; Gu, W.; Pandolfi, P. P.
Article Title: The function of PML in p53-dependent apoptosis
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.
Keywords: signal transduction; controlled study; nonhuman; animal cell; mouse; animal; mice; dna damage; apoptosis; protein dna binding; transcription initiation; neoplasm proteins; mice, mutant strains; gene function; in vivo study; in vitro study; protein p53; transcription factors; cancer inhibition; leukemia, promyelocytic, acute; gene expression regulation, neoplastic; transcription regulation; thymus gland; promyelocytic leukemia; gamma irradiation; cell nucleus; gene induction; gamma rays; trans-activation (genetics); cell nucleus inclusion body; priority journal; article; cell compartmentation; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title: Nature Cell Biology
Volume: 2
Issue: 10
ISSN: 1465-7392
Publisher: Nature Publishing Group  
Date Published: 2000-10-01
Start Page: 730
End Page: 736
Language: English
DOI: 10.1038/35036365
PUBMED: 11025664
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-0034306019&partnerID=40&md5=67c5d576a70f197e786527703f9dcf67
Notes: Export Date: 18 November 2015 -- Source: Scopus
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MSK Authors
  1. Paolo Salomoni
    21 Salomoni
  2. Sue Zhong
    17 Zhong
  3. Pier Paolo Pandolfi Derinaldis
    353 Pandolfi Derinaldis
  4. Alan H Shih
    59 Shih
  5. Ailan Guo
    4 Guo
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