The function of PML in p53-dependent apoptosis.
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.
Guo
A
A
Department of Human Genetics and Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Salomoni
P
P
Luo
J
J
Shih
A
A
Zhong
S
S
Gu
W
W
Pandolfi
P P
PP
D000818:Animals; D017209:Apoptosis; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000648:ultrastructure; D004249:DNA Damage; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins