Role of PTB-like protein, a neuronal RNA-binding protein, during the differentiation of PC12 cells
Role of PTB-like protein, a neuronal RNA-binding protein, during the differentiation of PC12 cells
复制标题
DOI：
10.1093/oxfordjournals.jbchem.a003176
复制
发表时间：
2002-06-01
影响因子：
2.7
通讯作者：
Yoshimura, N
中科院分区：
文献类型：
--
作者：
Ichikawa, M;Kikuchi, T;Yoshimura, N
PTB样蛋白（PTB-like protein，PTBLP）是嘧啶束结合蛋白（pyrimidine tract binding protein，PTB）的一个新的同源物，已被克隆为肿瘤相关性视网膜病变的一种可能的自身抗原。PTBLP具有两个功能域，核定位信号和RNA识别基序（RRM）。全长PTBLP（PTBLP-L）具有四个RRM，并且其可变剪接产物（PTBLP-S）缺少第三和第四RRM。虽然PTBLP在神经元组织中表达，但PTBLP的功能尚未确定。我们已经研究了PTBLP是否在使用PC 12细胞的神经元分化中起作用。在神经生长因子诱导PC 12细胞向神经元分化的过程中，PTBLP-L表达下调，PTBLP-S表达上调。将PTBLP-L转染入PC 12细胞导致神经元分化的抑制。然而，在PTBLP-S转染的细胞中，这种抑制并不明显。当PTBLP-L和PTBLP-S共转染时，PTBLP-L的抑制作用减弱。在分化的细胞中，PTBLP-S定位于细胞核，PTBLP-L被发现分散在整个细胞质和神经生长锥。这些结果表明，PTBLP-L作为神经元分化的负调节剂和PTBLP-S作为PTBLP-L的竞争者。
PTB-like protein (PTBLP) is a new homologue of pyrimidine tract binding protein (PTB), and has been cloned as a possible autoantigen in cancer-associated retinopathy. PTBLP has two functional domains, the nuclear localization signal and the RNA recognition motifs (RRMs). Full-length PTBLP (PTBLP-L) has four RRMs, and its alternative splicing product (PTBLP-S) lacks the third and fourth RRMs. Although PTBLPs are expressed in neuronal tissues, the function of PTBLPs has not been determined. We have studied whether PTBLP plays a role in neuronal differentiation using PC12 cells. During the process of nerve growth factor-induced neuronal differentiation of PC12 cells, PTBLP-L was down-regulated whereas PTBLP-S was up-regulated. Transfection of PTBLP-L into PC12 cells led to the suppression of neuronal differentiation. In PTBLP-S transfected cells, however, this suppression was not evident. When both PTBLP-L and PTBLP-S were co-transfected, the suppressive effect of PTBLP-L decreased. In differentiated cells, PTBLP-S localized in the nucleus and PTBLP-L was found dispersed throughout the cytoplasm and neuronal growth cone. These findings suggest that PTBLP-L acts as a negative regulator of neuronal differentiation and PTBLP-S acts as a competitor of PTBLP-L.