Splicing variant of Cdc42 interacting protein-4 disrupts β-catenin-mediated cell-cell adhesion:: Expression and function in renal cell carcinoma
Splicing variant of Cdc42 interacting protein-4 disrupts β-catenin-mediated cell-cell adhesion:: Expression and function in renal cell carcinoma
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DOI：
10.1016/j.bbrc.2005.11.117
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发表时间：
2006-01-27
影响因子：
3.1
通讯作者：
Saku, K
中科院分区：
文献类型：
--
作者：
Tsuji, E;Tsuji, Y;Saku, K
我们已经确定了一个选择性剪接变异的Cdc 42相互作用蛋白4（CIP 4）基因在肾细胞癌（RCC）患者，近50%的RCC检查显示异常剪接事件在逆转录PCR和插入的19个核苷酸来自内含子9的序列分析的基础上。这种变体（CIP 4-V）编码一个提前终止密码子，导致酪氨酸磷酸化位点、Cdc 42结合结构域和SH 3结构域的丢失。在这份报告中，我们表明，CIP 4-V的过度表达导致形成的泛素化侵略和细胞间粘附的损失。我们确定，CIP 4-V增加了介导Fer/Fyn酪氨酸激酶的β-连环蛋白酪氨酸磷酸化水平，并诱导β-连环蛋白从细胞膜向细胞质侵袭体的误激活。这些结果表明CIP 4对于β-连环蛋白介导的细胞-细胞粘附是至关重要的，并且可能是其对RCC的功能贡献的重要方面，特别是关于转移和侵袭性。(c)2005年爱思唯尔公司All rights reserved.
We have identified an alternative splicing variant in the Cdc42-interacting protein 4 (CIP4) gene in patients with renal cell carcinoma (RCC); almost 50% of the RCCs examined showed an aberrant splicing event in reverse transcription-PCR and the insertion of 19 nucleotides derived from intron9 based on a sequence analysis. This variant (CIP4-V) encodes a premature stop codon, resulting in the loss of a tyrosine phosphorylation site, the Cdc42 binding domain, and the SH3 domain. In this report, we show that overexpression of CIP4-V causes the formation of ubiquitinated aggresomes and a loss of cell-cell adhesion. We determined that CIP4-V increased the P-catenin tyrosine phosphorylation levels that mediate Fer/Fyn tyrosine kinases and induced beta-catenin mistrafficking from cell membrane to cytoplasmic aggresome. These results indicate that CIP4 is critical for beta-catenin-mediated cell-cell adhesion and may be an important aspect of its functional contribution to RCC, especially with regard to metastasis and invasiveness. (c) 2005 Elsevier Inc. All rights reserved.