RPAP3 splicing variant isoform 1 interacts with PIH1D1 to compose R2TP complex for cell survival.
RPAP3 splicing variant isoform 1 interacts with PIH1D1 to compose R2TP complex for cell survival.
复制标题
RPAP3 剪接变体亚型 1 与 PIH1D1 相互作用，组成 R2TP 复合物以维持细胞存活。
DOI：
10.1016/j.bbrc.2012.11.017
复制
发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Kamisaki Y.
中科院分区：
文献类型：
--
作者：
Yoshida M;Saeki M;Egusa H;Irie Y;Kamano Y;Uraguchi S;Sotozono M;Niwa H;Kamisaki Y.
我们之前将RNA聚合酶ii相关蛋白3 （RPAP3）定性为细胞死亡促进因子。本文报道了RPAP3的剪接异构体，异构体1和2的鉴定和表征。我们研究了RPAP3与PIH1结构域蛋白1 （PIH1D1）之间的相互作用，发现RPAP3亚型1与PIH1D1相互作用，而亚型2与PIH1D1不相互作用。此外，通过小干扰RNA敲低RPAP3亚型1可下调PIH1D1蛋白水平，但不影响PIH1D1 mRNA。RPAP3异构体2增强了阿霉素诱导的人乳腺癌T-47细胞死亡，但异构体1没有影响。这些结果表明R2TP复合体是由RPAP3的1型异构体组成的，RPAP3的2型异构体可能对R2TP复合体的存活能力有主要的负面影响。
We previously characterized RNA polymerase II-associated protein 3 (RPAP3) as a cell death enhancer. Here we report the identification and characterization of splicing isoform of RPAP3, isoform 1 and 2. We investigated the interaction between RPAP3 and PIH1 domain containing protein 1 (PIH1D1), and found that RPAP3 isoform 1, but not isoform 2, interacted with PIH1D1. Furthermore, knockdown of RPAP3 isoform 1 by small interfering RNA down-regulated PIH1D1 protein level without affecting PIH1D1 mRNA. RPAP3 isoform 2 potentiated doxorubicin-induced cell death in human breast cancer T-47 cells although isoform 1 showed no effect. These results suggest that R2TP complex is composed of RPAP3 isoform 1 for its stabilization, and that RPAP3 isoform 2 may have a dominant negative effect on the survival potency of R2TP complex.