Alternative titles; symbols
HGNC Approved Gene Symbol: CREBZF
Cytogenetic location: 11q14.1 Genomic coordinates (GRCh38) : 11:85,657,990-85,682,863 (from NCBI)
The herpes simplex virus (HSV) virion protein-16 (VP16) induces the transcription of HSV immediate-early genes by its association with OCT1 (POU2F1; 164175). This association, however, is unstable and requires the evolutionarily conserved host cell factor, HCFC1 (300019). The N and C termini of HCFC1 interact with each other and with VP16. Using a yeast 2-hybrid screen of a HeLa cell cDNA library with a fusion construct of the N and C termini of HCFC1 as bait in order to elucidate the normal cellular function of HCFC1, followed by EST database searching, Lu and Misra (2000) isolated a cDNA encoding Zhangfei (ZF). The authors named the protein Zhangfei after a legendary warrior who was a contemporary of Luman (CREB3; 606443) in ancient China. Sequence analysis predicted that the 272-amino acid ZF protein has a negatively charged N terminus, a basic domain and a leucine zipper of 6 heptad leucine repeats separated by a conserved 6-amino acid spacer, and a bZIP region. Functional analysis showed that the N-terminal acidic region is an activation domain. EMSA analysis indicated, however, that ZF could not activate bZIP-type promoters, possibly due to an N-terminal conformational change resulting from the lack of a critical asn residue. Functional and binding analyses indicated that ZF interacted with HCFC1 without interfering with VP16 binding, whereas 3 ZF mutants did not interact with HCFC1. In addition, most cells expressing ZF appeared to be nonpermissive for HSV infection. Northern blot analysis revealed an approximately 4.6-kb ZF transcript that was abundant in heart, liver, and skeletal muscle, moderate in kidney and pancreas, barely detectable in lung, and not expressed in brain. Expression was high in fetal kidney but low in heart, lung, and liver. No protein could be detected in tissues or cell lines by Western blot analysis. Lu and Misra (2000) proposed that the role of ZF as an HCFC1-binding factor suggests that HCFC1 may regulate the activity of several transcription factors and that alpha viruses such as HSV may have evolved to exploit this mechanism.
By electronic PCR, Lu and Misra (2000) mapped the ZF gene to 11q14.1.
Lu, R., Misra, V. Zhangfei: a second cellular protein interacts with herpes simplex virus accessory factor HCF in a manner similar to Luman and VP16. Nucleic Acids Res. 28: 2446-2454, 2000. [PubMed: 10871379] [Full Text: https://doi.org/10.1093/nar/28.12.2446]