Calsenilin interacts with transcriptional co-repressor C-terminal binding protein(s).
Calsenilin interacts with transcriptional co-repressor C-terminal binding protein(s).
复制标题
Calsenilin 与转录共阻遏物 C 端结合蛋白相互作用。
DOI：
10.1111/j.1471-4159.2006.03972.x
复制
发表时间：
2006
影响因子：
4.7
通讯作者：
Wasco,Wilma
中科院分区：
文献类型：
--
作者：
Zaidi,NikhatF;Kuplast,KristyG;Washicosky,KevinJ;Kajiwara,Yuji;Buxbaum,JosephD;Wasco,Wilma
钙生蛋白/钾通道相互作用蛋白(KChIP)3/下游调节元件序列拮抗剂调节剂(DREAM)是一种神经元钙结合蛋白，在细胞内具有多种功能，包括调节早老素的加工、抑制转录和调节A型钾通道。为了更好地了解钙调素在特定细胞间隔中的确切作用，进行了一项相互作用的寻找与钙调素N-末端结构域结合的蛋白质。利用酵母双杂交系统和免疫共沉淀研究，我们已经确定转录共抑制因子C-末端结合蛋白(CtBP)2是钙调素的相互作用蛋白，并表明这两种蛋白可以在体内相互作用。在免疫共沉淀研究中，钙黄素还与CtBP2同源物CtBP1相互作用。我们的数据还显示，在CtBP基因敲除的成纤维细胞中，c-fos蛋白水平随钙调素的增加而增加，提示CtBP可能通过钙调素调节c-fos的转录抑制。此外，组蛋白脱乙酰酶蛋白和活性与钙生蛋白-CtBP免疫复合体相关的发现提示了钙生蛋白-CtBP可能抑制转录的机制。最后，我们证明了Calsenin和CtBP存在于突触小泡中，并可以与体内相互作用。
Calsenilin/potassium channel‐interacting protein (KChIP)3/ downstream regulatory element sequence antagonist modulator (DREAM) is a neuronal calcium‐binding protein that has been shown to have multiple functions in the cell, including the regulation of presenilin processing, repression of transcription and modulation of A‐type potassium channels. To gain a better understanding of the precise role of calsenilin in specific cellular compartments, an interactor hunt for proteins that bind to the N‐terminal domain of calsenilin was carried out. Using a yeast two‐hybrid system and co‐immunoprecipitation studies, we have identified the transcriptional co‐repressor C‐terminal binding protein (CtBP)2 as an interactor for calsenilin and have shown that the two proteins can interactin vivo. In co‐immunoprecipitation studies, calsenilin also interacted with CtBP1, a CtBP2 homolog. Our data also showed a calsenilin‐dependent increase in c‐fos protein levels in CtBP knockout fibroblasts, suggesting that CtBP may modulate the transcriptional repression ofc‐fosby calsenilin. Furthermore, the finding that histone deacetylase protein and activity were associated with the calsenilin–CtBP immunocomplex suggests a mechanism by which calsenilin–CtBP may act to repress transcription. Finally, we demonstrated that calsenilin and CtBP are present in synaptic vesicles and can interactin vivo.