CARM1 Activates Myogenin Gene via PCAF in the Early Differentiation of TPA-Induced Rhabdomyosarcoma-Derived Cells
CARM1 Activates Myogenin Gene via PCAF in the Early Differentiation of TPA-Induced Rhabdomyosarcoma-Derived Cells
复制标题
CARM1 在 TPA 诱导的横纹肌肉瘤衍生细胞的早期分化中通过 PCAF 激活肌生成素基因
DOI：
10.1002/jcb.22522
复制
发表时间：
2010-05-01
影响因子：
4
通讯作者：
Shen, Yu-fei
中科院分区：
文献类型：
--
作者：
Gao, Xin;Pan, Wei-song;Shen, Yu-fei
CARM 1/PRMT 4是蛋白质精氨酸甲基转移酶（PRMT）家族的成员。CARM 1作为一种转录辅激活因子，在哺乳动物基因中发挥着积极的作用。在这里，我们表明，CARM 1可以招募到肌细胞生成素基因的启动子，以增强其转录激活通过PCAF在TPA诱导的RD细胞分化的早期阶段。加入腺苷二醛。AdOx抑制RD细胞中的PRMT，TPA诱导的p300、PCAF和肌细胞生成素启动子处的Brg 1的募集被消除，并且肌细胞生成分化被阻断。更具体地，当CARM 1被其特异性siRNA敲低时，PCAF的表达及其成核被抑制。我们认为CARM 1和PCAF的物理相互作用可能是CARM 1通路下游PCAF激活的关键，从而在TPA诱导的分化下诱导肌细胞生成素。这些发现为横纹肌肉瘤患者的治疗提供了新的治疗靶点。J.细胞。110：162-170，2010. (C)2010 Wiley-Liss，Inc.
CARM1/PRMT4 is a member of the protein arginine methyltransferase (PRMT) family. CARM1 as a transcriptional coactivator plays an active role on mammalian genes. Here, we show that CARM1 can be recruited to the promoter of myogenin gene to enhance its transcriptional activation via PCAF at the early stage of TPA-induced RD cell differentiation. By adding adenosine dialdehyde. AdOx, to inhibit the PRMT in RD cells, the TPA-induced recruiting of p300, PCAF and the Brg1 at the myogenin promoter is abolished and myogenic differentiation is blocked. More specifically, the expression of PCAF and its nucleation are prohibited when CARM1 is knockdown by its specific siRNA. We suggest that the physical interaction of CARM1 and PCAF is likely pivotal for the activation of PCAF in the downstream of CARM1 pathway for inducing myogenin under TPA-induced differentiation. The findings shed lights on novel therapeutic targets in the treatment of rhabdomyosarcoma patients. J. Cell. Biochem. 110: 162-170, 2010. (C) 2010 Wiley-Liss, Inc.