Vives Virginie, Su Jian, Zhong Shan, Ratnayaka Indrika, Slee Elizabeth, Goldin Robert, Lu Xin
Ludwig Institute for Cancer Research, University College London, London W1W 7BS, United Kingdom.
Genes Dev. 2006 May 15;20(10):1262-7. doi: 10.1101/gad.374006.
ASPP2 stimulates the apoptotic function of the p53 family in vivo. We show here that ASPP2-/- pups died before weaning. This postnatal lethality was significantly enhanced in p53+/- background and both deletions are synthetic lethal. ASPP2+/- mice developed spontaneous tumors. The tumor onset was accelerated by gamma-irradiation or in p53+/- background. Tumors derived from ASPP2+/- mice retained wild-type ASPP2 allele even though some of them lost p53. These provide the first genetic evidence that ASPP2 is a haploinsufficient tumor suppressor that shares overlapping function(s) with p53 in mouse development and tumor suppression.
ASPP2在体内刺激p53家族的凋亡功能。我们在此表明，ASPP2基因敲除的幼崽在断奶前死亡。这种出生后致死率在p53杂合背景下显著增强，且两种缺失是合成致死的。ASPP2杂合小鼠会自发形成肿瘤。γ射线照射或在p53杂合背景下会加速肿瘤发生。源自ASPP2杂合小鼠的肿瘤保留了野生型ASPP2等位基因，尽管其中一些失去了p53。这些提供了首个遗传学证据，表明ASPP2是一种单倍剂量不足的肿瘤抑制因子，在小鼠发育和肿瘤抑制方面与p53具有重叠功能。
