The function of PML in p53-dependent apoptosis

@article{Guo2000TheFO,
  title={The function of PML in p53-dependent apoptosis},
  author={Ailan Guo and Paolo Salomoni and Jianyuan Luo and Alan H. Shih and Sue Zhong and Wei Gu and Pier Paolo Pandolfi},
  journal={Nature Cell Biology},
  year={2000},
  volume={2},
  pages={730-736}
}
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… 
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TLDR
It is shown that complete Pml inactivation, in a context of p53 heterozygosity, redistributes and expands the tumor spectrum leading to the formation of angiosarcomas and increased lymphomagenesis.
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TLDR
Earlier and recent advances on the molecular mechanisms by which PML regulates apoptosis are summarized and the implication of these findings for cancer pathogenesis is summarized.
Promyelocytic Leukemia Is a Direct Inhibitor of SAPK2/p38 Mitogen-activated Protein Kinase*
TLDR
A novel function of PML is defined as a negative regulator of p38 kinase, suggesting that PML might regulate apoptosis through manipulating SAPK2/p38 pathways.
The Promyelocytic Leukemia Protein Protects p53 from Mdm2-mediated Inhibition and Degradation*
TLDR
The role of the promyelocytic leukemia protein (PML) in the activation of p53 in response to stress is investigated and it is found that PML is critical for the accumulation of p 53 in Response to DNA damage under physiological conditions.
A Cytoplasmic PML Mutant Inhibits p53 Function
TLDR
It is reported that cy toplasmic PML is able to induce the relocation of nPML to the cytoplasm, thus reducing the number of PML-NBs, and remarkable, Mut PML inhibits p53 transcriptional, growth suppressive, and apoptotic functions, thus suggesting that cytopLasmic expression ofPML has an impact on survival through inhibition of nuclear PML.
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TLDR
It is demonstrated that a catalytically active form of the mammalian E3 ligase E6AP (HPV E6-associated protein) acts to reduce the half-life of the PML protein by promoting its degradation in the proteasome.
PML is a direct p53 target that modulates p53 effector functions.
AXIN is an essential co-activator for the promyelocytic leukemia protein in p53 activation
TLDR
It is shown that AXin interacts with PML in vivo, and further that AXIN, PML and p53 form a ternary complex, and thatAXIN promotes PML sumoylation, a modification necessary for PML functions.
The promyelocytic leukemia protein PML regulates c-Jun function in response to DNA damage.
TLDR
It is shown that PML selectively regulates proapoptotic transcription factors upon different types of DNA damage and that Pml inactivation protects fibroblasts from UV-induced apoptosis in a p53-independent manner.
Perspectives in PML: a unifying framework for PML function.
TLDR
A possible molecular model of PML function is postulate that could provide a unifying underpinning for many of its disparate activities and explores how the ability ofPML to coordinately and combinatorially regulate gene expression post-transcriptionally, enables PML to have such broad ranging effects on cellular physiology.
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