National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
J Cell Biochem. 2010 May;110(1):162-70. doi: 10.1002/jcb.22522.
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.
CARM1/PRMT4 是蛋白精氨酸甲基转移酶（PRMT）家族的成员。CARM1 作为转录共激活因子，在哺乳动物基因中发挥着积极的作用。在这里，我们表明 CARM1 可以被招募到肌生成素基因的启动子上，通过 PCAF 在 TPA 诱导的 RD 细胞分化的早期增强其转录激活。通过在 RD 细胞中添加腺嘌呤二醛（AdOx）抑制 PRMT，TPA 诱导的 p300、PCAF 和 Brg1 在肌生成素启动子上的募集被阻断，肌生成分化被阻断。更具体地说，当用其特异性 siRNA 敲低 CARM1 时，PCAF 的表达及其核形成被抑制。我们认为，在 CARM1 通路下游，CARM1 和 PCAF 的物理相互作用可能对 PCAF 的激活至关重要，从而在 TPA 诱导的分化过程中诱导肌生成素的表达。这些发现为治疗横纹肌肉瘤患者提供了新的治疗靶点。
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