抑制损伤调节自噬调节剂-1（DRAM-1）可损害 NB4APL 细胞的中性粒细胞分化。
Inhibition of damage-regulated autophagy modulator-1 (DRAM-1) impairs neutrophil differentiation of NB4 APL cells.
机构信息
Experimental Oncology/Hematology, Department of Clinical Research, University of Bern, Bern, Switzerland.
出版信息
Leuk Res. 2012 Dec;36(12):1552-6. doi: 10.1016/j.leukres.2012.08.024. Epub 2012 Sep 13.
The damage-regulator autophagy modulator 1 (DRAM-1) is a lysosomal protein that positively regulates autophagy in a p53-dependent manner. We aimed at analyzing the role of DRAM-1 in granulocytic differentiation of APL cells. We observed a significant increase of DRAM-1 expression during all-trans retinoic acid (ATRA)-induced neutrophil differentiation of NB4 APL cells but not in ATRA-resistant NB4-R2 cells. Next, knocking down DRAM-1 in NB4 APL cells was sufficient to impair neutrophil differentiation. Given that DRAM-1 is a transcriptional target of p53, we tested if DRAM-1 is regulated by the p53 relative p73. Indeed, inhibiting p73 prevented neutrophil differentiation and DRAM-1 induction of NB4 cells. In conclusion, we show for the first time that p73-regulated DRAM-1 is functionally involved in neutrophil differentiation of APL cells.
损伤调控自噬调节剂 1（DRAM-1）是一种溶酶体蛋白，它以依赖 p53 的方式正向调节自噬。我们旨在分析 DRAM-1 在 APL 细胞粒细胞分化中的作用。我们观察到，在全反式视黄酸（ATRA）诱导的 NB4 APL 细胞中性粒细胞分化过程中，DRAM-1 的表达显著增加，但在 ATRA 耐药的 NB4-R2 细胞中没有增加。接下来，在 NB4 APL 细胞中敲低 DRAM-1 足以损害中性粒细胞分化。鉴于 DRAM-1 是 p53 的转录靶标，我们测试了 DRAM-1 是否受 p53 相对 p73 的调节。事实上，抑制 p73 可阻止 NB4 细胞的中性粒细胞分化和 DRAM-1 诱导。总之，我们首次表明，p73 调节的 DRAM-1 功能上参与了 APL 细胞的中性粒细胞分化。
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