The p53 tumour suppressor inhibits glucocorticoid-induced proliferation of erythroid progenitors
The p53 tumour suppressor inhibits glucocorticoid-induced proliferation of erythroid progenitors
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DOI：
10.1093/embo-reports/kvf114
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发表时间：
2002-06-01
期刊：
影响因子：
7.7
通讯作者：
Wasylyk, B
中科院分区：
文献类型：
--
作者：
Ganguli, G;Back, J;Wasylyk, B
高海拔缺氧、失血和红细胞白血病引发应激性红细胞生成，涉及糖皮质激素诱导的红细胞祖细胞（ebls）增殖。肿瘤抑制因子p53刺激造血细胞成熟并在缺氧时拮抗糖皮质激素受体（GR）活性，提示其可能抑制应激性红细胞生成。我们报道缺乏p53的小鼠胎儿肝细胞在GR激动剂地塞米松存在下比野生型细胞增殖更好。gr诱导ebl自我更新的一个重要媒介，c-myb基因，被地塞米松诱导到p53(-/-) ebl中较高水平。在p53（-/-）小鼠的脾脏中，对贫血的应激反应更快，表现为集落形成单位红细胞水平较高，CD34/c-kit双阳性群体增加。我们的研究结果表明，p53可拮抗gr介导的ebl扩增，并首次证明p53- gr串扰在体内应激性红细胞生成这一生理过程中起重要作用。
Hypoxia encountered at high altitude, blood loss and erythroleukemia instigate stress erythropoiesis, which involves glucocorticoid-induced proliferation of erythroid progenitors (ebls). The tumour suppressor p53 stimulates hematopoietic cell maturation and antagonizes glucocorticoid receptor (GR) activity in hypoxia, suggesting that it may inhibit stress erythropoiesis. We report that mouse fetal liver ebls that lack p53 proliferate better than wild-type cells in the presence of the GR agonist dexamethasone. An important mediator of GR-induced ebl self-renewal, the c-myb gene, is induced to higher levels in p53(-/-) ebls by dexamethasone. The stress response to anemia is faster in the spleens of p53(-/-) mice, as shown by the higher levels of colony forming units erythroids and the increase in the CD34/c-kit double positive population. Our results show that p53 antagonizes GR-mediated ebl expansion and demonstrate for the first time that p53-GR cross-talk is important in a physiological process in vivo: stress erythropoiesis.