Identification and genetic analysis of human and mouse activated Cdc42 interacting protein-4 isoforms

Identification and genetic analysis of human and mouse activated Cdc42 interacting protein-4 isoforms
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DOI:
10.1016/s0006-291x(02)00398-4
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发表时间:
2002-05-24
影响因子:
3.1
通讯作者:
Corey, S
Corey, S
中科院分区:
生物学4区
文献类型:
--
作者:
Wang, L;Rudert, WA;Corey, S

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以Src激酶Lyn为诱饵,通过酵母双杂交筛选,鉴定出一个具有支架蛋白特征的新基因产物。报道为Felic (fes相关,与Ezrin同源,Lyn与Cdc42相互作用),与CIP4 (Cdc42相互作用蛋白-4)基因有关。基因组DNA CIP4/Felic的Southern印迹显示为单带,提示无基因重复。Felic与CIP4的不同之处在于内含子13的3'端有一个29个核苷酸的序列。因此,存在破坏SH3域的帧外转换。对不同组织的分析表明,原始CIP4是主要转录本。因此,我们建议将其命名为CIP4a,将Felic命名为CIP4b。在结肠直肠癌cco2细胞系筛选过程中,鉴定出了第三个cip4相关转录物(CIP4c)对应的克隆。CIP4c编码一个过早停止密码子,导致SH3结构域的丢失。第四个相对丰富的转录物(CIP4h)从心脏、肺和气管组织中分离出来。CIP4h保留了SH3结构域。CIP4水平被全反式维甲酸改变。有或没有SH3结构域的可选剪接转录本的存在表明,CIP4以组织特异性的方式通过结构功能差异调节细胞骨架组织。(C) 2002 Elsevier Science (USA)。版权所有。
By yeast two-hybrid screening with the Src kinase Lyn as bait, we identified a novel gene product with features of a scaffolding protein. Reported as Felic (Fes-related, with homology to Ezrin, Lyn interactor with Cdc42), it is related to the CIP4 (Cdc42 Interacting Protein-4) gene. Southern blotting for CIP4/Felic of genomic DNA shows a single band, suggesting no gene duplication. Felic differs from CIP4 because of a 29 nucleotide sequence derived from the 3' end of intron 13. Consequently, there is an out-of-frame translation that destroys an SH3 domain. Analysis of various tissues shows that the original CIP4 is the predominant transcript. Therefore, we propose to call that, CIP4a and Felic, CIP4b. During screening of the colorectal CaCo2 cell line, clones corresponding to a third CIP4-related transcript (CIP4c) were identified. CIP4c encodes a premature stop codon, resulting in the loss of the SH3 domain. A fourth, relatively abundant transcript (CIP4h) was isolated from heart, lung, and trachea tissue. CIP4h retains the SH3 domain. CIP4 levels are modified by all-trans-retinoic acid. The presence of alternative splice transcripts, with or without SH3 domains, suggests that CIP4 regulates cytoskeletal organization through structural-functional differences in a tissue-specific manner. (C) 2002 Elsevier Science (USA). All rights reserved.