Role of PML in cell growth and the retinoic acid pathway.
Role of PML in cell growth and the retinoic acid pathway.
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DOI：
10.1126/science.279.5356.1547
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发表时间：
1998-03
期刊：
影响因子：
56.9
通讯作者：
Zhugang Wang;L. Delva;M. Gaboli;R. Rivi;M. Giorgio;C. Cordon-Cardo;F. Grosveld;P. Pandolfi
中科院分区：
文献类型：
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作者：
Zhugang Wang;L. Delva;M. Gaboli;R. Rivi;M. Giorgio;C. Cordon-Cardo;F. Grosveld;P. Pandolfi
在与急性早幼粒细胞白血病（APL）相关的染色体易位中，PML基因与视黄酸受体α (rar α)基因融合。用同源重组法消融小鼠PML蛋白，发现PML调节造血分化，控制细胞生长和肿瘤发生。PML功能对于维甲酸（RA）的肿瘤生长抑制活性及其诱导前体细胞末梢髓系分化的能力至关重要。PML是ra依赖的p21WAF1/CIP1基因的转激活所必需的，该基因调节细胞周期进程和细胞分化。这些结果表明PML是RA通路的一个关键组成部分，PML- rar α融合蛋白破坏其活性可能在APL发病机制中很重要。
The PML gene is fused to the retinoic acid receptor alpha (RARalpha) gene in chromosomal translocations associated with acute promyelocytic leukemia (APL). Ablation of murine PML protein by homologous recombination revealed that PML regulates hemopoietic differentiation and controls cell growth and tumorigenesis. PML function was essential for the tumor-growth-suppressive activity of retinoic acid (RA) and for its ability to induce terminal myeloid differentiation of precursor cells. PML was needed for the RA-dependent transactivation of the p21WAF1/CIP1 gene, which regulates cell cycle progression and cellular differentiation. These results indicate that PML is a critical component of the RA pathway and that disruption of its activity by the PML-RARalpha fusion protein may be important in APL pathogenesis.