p53-p21通路抑制组蛋白甲基转移酶NSD2的表达

p53-p21 Pathway Inhibits Expression of the Histone Methyltransferase NSD2

NSD2(nuclear receptor-binding SET domain 2)是一种在黑色素瘤等多种肿瘤细胞中高表达的组蛋白甲基转移酶,其在Wolf-Hirschhorn综合症(wolf-Hirschhorn syndrome,WHS)和多发性骨髓瘤(multiple myeloma,MM)疾病中表达异常的原因已经得到了较好的阐明。而NSD2在其它肿瘤中的表达为何失调还未阐明。本研究选用p53野生型的恶性黑色素瘤细胞系92-1作为细胞模型,采用DNA损伤试剂依托泊苷处理和RNA干扰技术,通过定量PCR和蛋白质免疫印迹的方法首次证实了p53-p21通路对NSD2具有抑制作用。

Nuclear Receptor-binding SET Domain 2（ NSD2） is a histone methyltransferase that is reported out of control in Wolf-Hirschhorn syndrome（ WHS） and many carcinoma cells including melanoma. However, except for the studies in WHS and multiple myeloma（MM） , little is known about the mechanism that is responsible for its abnormal expression. Here, DNA damage agent etoposide and RNA interference were used to explore whether p53-p21 pathway affected the NSD2 expression in a p53 wild type myeloma cell line 92-1. It was found that p53 or p21 inhibited NSD2 expression. This is the first publication that relates p53-p21 pathway with NSD2 dysregulation.