De-dimerization of PTB is catalyzed by PDI and is involved in the regulation of p53 translation.
De-dimerization of PTB is catalyzed by PDI and is involved in the regulation of p53 translation.
复制标题
DOI：
10.1093/nar/gkab708
复制
发表时间：
2021-09-20
影响因子：
14.9
通讯作者：
Xiao R
中科院分区：
文献类型：
--
作者：
Gong FX;Zhan G;Han R;Yang Z;Fu X;Xiao R
多聚嘧啶结合蛋白(PTB)是一种RNA结合蛋白，以二聚体和单体形式存在，穿梭于胞核和胞浆之间。然而，PTB二聚化的调控及其功能与亚细胞定位之间的关系尚不清楚。我们发现PTB在胞核和胞浆中分别以二聚体和单体的形式存在，半胱氨酸23的二硫键对PTB的二聚化起关键作用。此外，蛋白质二硫键异构酶(PDI)被确定为催化PTB解聚的酶，这取决于PDI的a‘结构域的CGHC活性部位。此外，在拓扑异构酶抑制剂诱导DNA损伤时，PTB被证明是二聚化的，胞浆内积累。最后，细胞质PTB被发现与核糖体相关，并增强P53的翻译。总而言之，这些发现揭示了以前未知的PTB二聚化机制，并揭示了PTB二聚化在功能上与细胞质定位和翻译调节有关。
Polypyrimidine tract-binding protein (PTB) is an RNA binding protein existing both as dimer and monomer and shuttling between nucleus and cytoplasm. However, the regulation of PTB dimerization and the relationship between their functions and subcellular localization are unknown. Here we find that PTB presents as dimer and monomer in nucleus and cytoplasm respectively, and a disulfide bond involving Cysteine 23 is critical for the dimerization of PTB. Additionally, protein disulfide isomerase (PDI) is identified to be the enzyme that catalyzes the de-dimerization of PTB, which is dependent on the CGHC active site of the a’ domain of PDI. Furthermore, upon DNA damage induced by topoisomerase inhibitors, PTB is demonstrated to be de-dimerized with cytoplasmic accumulation. Finally, cytoplasmic PTB is found to associate with the ribosome and enhances the translation of p53. Collectively, these findings uncover a previously unrecognized mechanism of PTB dimerization, and shed light on the de-dimerization of PTB functionally linking to cytoplasmic localization and translational regulation.
登录
查看更多内容
影响因子：
5.6
作者：
Kim, JH;Hahm, B;Jang, SK
通讯作者：
Jang, SK
影响因子：
14.9
作者：
Katoch A;George B;Iyyappan A;Khan D;Das S
通讯作者：
Das S
DOI：
10.1073/pnas.88.19.8740
发表时间：
1991-10-01
影响因子：
11.1
作者：
BERGER, NA;CHATTERJEE, S;HELMS, SR
通讯作者：
HELMS, SR
影响因子：
8
作者：
Grover, R.;Candeias, M. M.;Das, S.
通讯作者：
Das, S.
影响因子：
4.8
作者：
Pirneskoski, A;Klappa, P;Ruddock, LW
通讯作者：
Ruddock, LW