Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W, Pandolfi P P
Department of Human Genetics and Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nat Cell Biol. 2000 Oct;2(10):730-6. doi: 10.1038/35036365.
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.
急性早幼粒细胞白血病（APL）的PML基因编码一种生长抑制和肿瘤抑制蛋白，该蛋白对于多种凋亡信号至关重要。PML发挥其促凋亡功能的机制仍不清楚。在此我们表明，PML作为p53的转录共激活因子发挥作用。PML在体外和体内均与p53发生物理相互作用，并与p53在PML核体（PML-NB）中共定位。PML的共激活作用取决于其定位于PML-NB的能力。在PML基因敲除的原代细胞中，p53依赖的、DNA损伤诱导的凋亡、p53的转录激活、p53的DNA结合能力以及γ射线照射后p53靶基因如Bax和p21的诱导均受损。这些结果定义了一条新的依赖PML的、p53调节的凋亡途径，并为PML在肿瘤抑制中的功能提供了新的线索。
