Molecular properties of Zic4 and Zic5 proteins: functional diversity within Zic family.
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.
Laboratory for Comparative Neurogenesis, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198, Japan.
Akira
A
Ishiguro
Takashi
T
Inoue
Katuhiko
K
Mikoshiba
Jun
J
Aruga
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D041681:NIH 3T3 Cells; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D018006:Myogenic Regulatory Factors; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C491811:Zic2 protein, mouse; C100431:Zic4 protein, mouse; C418623:Zic5 protein, mouse; D004247:DNA