The PML gene of acute promyelocytic leukaemia (APL) encodes a growth- and t
umour-suppresor protein that is essential for several apoptotic signals. Th
e mechanisms by which PML exerts its pro-apoptotic function are still unkno
wn. Here we show that PML acts as a transcriptional cc-activator with p53.
PML physically interacts with p53 both in vitro and in vivo and co-localize
s 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 abil
ity of p53, and the induction of p53 target genes such as Bar and p21 upon
gamma-irradiation are all impaired in PML-/- primary cells. These results d
efine a new PML-dependent, p53-regulatory pathway for apoptosis and shed ne
w light on the function of PML in tumour suppression.