Ishiguro Akira, Inoue Takashi, Mikoshiba Katuhiko, Aruga Jun
Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198, Japan.
Biochem Biophys Res Commun. 2004 Nov 5;324(1):302-7. doi: 10.1016/j.bbrc.2004.09.052.
The Zic-family proteins control various developmental processes. Previous studies have shown that Zic1, Zic2, and Zic3 can act as transcriptional regulators, and that their functions are repressed by I-mfa, which has been identified as a repressor for basic helix-loop-helix-type transcriptional factors. Here, we investigated the molecular properties of the Zic4 and Zic5 proteins. Zic4/Zic5 showed DNA-binding activity to the Gli-binding sequence, similar to Zic1/Zic2/Zic3 proteins. However, Zic4/Zic5 did not exhibit any significant transcriptional activation ability nor they bind to I-mfa differently from Zic1/Zic2/Zic3. The nuclear localization of Zic4/Zic5 was not affected by the presence of the I-mfa protein, whereas the Zic1/Zic2/Zic3 proteins were translocated to the cytoplasmic compartment in the presence of I-mfa. The difference may be attributable to the dissimilarity of the N-terminal region between the Zic1/Zic2/Zic3 and Zic4/Zic5 proteins, since the binding of the Zic1/Zic2/Zic3 proteins to I-mfa occurs through their N-terminal regions.
锌指蛋白家族（Zic-family）蛋白控制着各种发育过程。先前的研究表明，Zic1、Zic2和Zic3可作为转录调节因子，且它们的功能受到I-mfa的抑制，I-mfa已被确定为一种针对碱性螺旋-环-螺旋型转录因子的抑制因子。在此，我们研究了Zic4和Zic5蛋白的分子特性。与Zic1/Zic2/Zic3蛋白相似，Zic4/Zic5对Gli结合序列显示出DNA结合活性。然而，Zic4/Zic5没有表现出任何显著的转录激活能力，并且它们与I-mfa的结合方式与Zic1/Zic2/Zic3并无不同。Zic4/Zic5的核定位不受I-mfa蛋白存在的影响，而在I-mfa存在的情况下，Zic1/Zic2/Zic3蛋白会转移到细胞质区室。这种差异可能归因于Zic1/Zic2/Zic3与Zic4/Zic5蛋白N端区域的不同，因为Zic1/Zic2/Zic3蛋白与I-mfa的结合是通过它们的N端区域发生的。
