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Guo, A, Salomoni, P, Luo, J, Shih, A, Zhong, S, Gu, W and Pandolfi, PP (2000) The function of PML in p53-dependent apoptosis. Nat. Cell Biol. 2:730-6
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.
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; Signal Transduction; Thymus Gland/cytology; Transcription Factors/genetics; Transcription Factors/metabolism; Transcriptional Activation; Tumor Suppressor Protein p53/metabolism; Tumor Suppressor Proteins
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