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Zhangfei is a potent and specific inhibitor of the host cell factor-binding transcription factor Luman.

Host cell factor (HCF) was initially discovered as a cellular co-factor required for the activation of herpes simplex virus immediate early gene expression by the virion associated transactivator VP16. HCF also participates in a variety of cellular processes, although the mechanism of its action is not known. VP16 binds to HCF through a 4-amino acid motif (EHAY), which closely resembles the HCF binding domain of two cellular basic leucine-zipper proteins, Luman and Zhangfei. Luman is a powerful transcription factor that, in transient expression assays, activates promoters containing cAMP or unfolded protein response elements (UPRE). In contrast, Zhangfei neither binds consensus recognition elements for basic leucine-zipper proteins nor does it activate promoters containing them. Here we show that Zhangfei suppresses the ability of Luman to activate transcription. HCF appeared to be required for efficient suppression. A mutant of Zhangfei, which was unable to bind HCF, was impaired in its ability to suppress Luman. Zhangfei did not suppress ATF6, a transcription factor closely related to Luman but that does not bind HCF, unless the HCF binding motif of Luman was grafted onto it. Zhangfei inhibited the HCF-dependent activation of a UPRE-containing promoter by a Gal4-Luman fusion protein but was unable to inhibit the HCF-independent activation by Gal4-Luman of a promoter that contained Gal4 binding motifs. Binding of HCF by Zhangfei was required for the co-localization of Luman and Zhangfei to nuclear domains, suggesting that HCF might target the proteins to a common location.

Pubmed ID: 15705566

Authors

  • Misra V
  • Rapin N
  • Akhova O
  • Bainbridge M
  • Korchinski P

Journal

The Journal of biological chemistry

Publication Data

April 15, 2005

Associated Grants

None

Mesh Terms

  • Adenoviridae
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Basic-Leucine Zipper Transcription Factors
  • Binding Sites
  • Cell Line
  • Cell Nucleus
  • Cyclic AMP
  • Cyclic AMP Response Element-Binding Protein
  • DNA, Complementary
  • DNA-Binding Proteins
  • Dose-Response Relationship, Drug
  • Genetic Vectors
  • Herpes Simplex Virus Protein Vmw65
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Leucine
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oligonucleotide Array Sequence Analysis
  • Plasmids
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • RNA
  • Response Elements
  • Transcription Factors
  • Transcription, Genetic
  • Transfection
  • Tumor Suppressor Proteins