This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mahajan, S. S.
Right arrow Articles by Wilson, A. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mahajan, S. S.
Right arrow Articles by Wilson, A. C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2000, p. 919-928, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Mutations in Host Cell Factor 1 Separate Its Role in Cell Proliferation from Recruitment of VP16 and LZIP

Shahana S. Mahajan and Angus C. Wilson*

Department of Microbiology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016

Received 8 September 1999/Returned for modification 13 October 1999/Accepted 1 November 1999

Host cell factor 1 (HCF-1) is a nuclear protein required for progression through G1 phase of the cell cycle and, via its association with VP16, transcriptional activation of the herpes simplex virus immediate-early genes. Both functions require a six-bladed beta -propeller domain encoded by residues 1 to 380 of HCF-1 as well as an additional amino-terminal region. The beta -propeller domain is well conserved in HCF homologues, consistent with a critical cellular function. To date, the only known cellular target of the beta -propeller is a bZIP transcription factor known as LZIP or Luman. Whether the interaction between HCF-1 and LZIP is required for cell proliferation remains to be determined. In this study, we used directed mutations to show that all six blades of the HCF-1 beta -propeller contribute to VP16-induced complex assembly, association with LZIP, and cell cycle progression. Although LZIP and VP16 share a common tetrapeptide HCF-binding motif, our results reveal profound differences in their interaction with HCF-1. Importantly, with several of the mutants we observe a poor correlation between the ability to associate with LZIP and promote cell proliferation in the context of the full HCF-1 amino terminus, arguing that the HCF-1 beta -propeller domain must target other cellular transcription factors in order to contribute to G1 progression.


* Corresponding author. Mailing address: Department of Microbiology, 550 First Ave., New York, NY 10016. Phone: (212) 263-0206. Fax: (212) 263-8276. E-mail: wilsoa02{at}popmail.med.nyu.edu.


Molecular and Cellular Biology, February 2000, p. 919-928, Vol. 20, No. 3
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Minakhina, S., Druzhinina, M., Steward, R. (2007). Zfrp8, the Drosophila ortholog of PDCD2, functions in lymph gland development and controls cell proliferation. Development 134: 2387-2396 [Abstract] [Full Text]  
  • Vogel, J. L., Kristie, T. M. (2006). Site-specific proteolysis of the transcriptional coactivator HCF-1 can regulate its interaction with protein cofactors. Proc. Natl. Acad. Sci. USA 103: 6817-6822 [Abstract] [Full Text]  
  • Akhova, O., Bainbridge, M., Misra, V. (2005). The Neuronal Host Cell Factor-Binding Protein Zhangfei Inhibits Herpes Simplex Virus Replication. J. Virol. 79: 14708-14718 [Abstract] [Full Text]  
  • Misra, V., Rapin, N., Akhova, O., Bainbridge, M., Korchinski, P. (2005). Zhangfei Is a Potent and Specific Inhibitor of the Host Cell Factor-binding Transcription Factor Luman. J. Biol. Chem. 280: 15257-15266 [Abstract] [Full Text]  
  • Khurana, B., Kristie, T. M. (2004). A Protein Sequestering System Reveals Control of Cellular Programs by the Transcriptional Coactivator HCF-1. J. Biol. Chem. 279: 33673-33683 [Abstract] [Full Text]  
  • Piluso, D., Bilan, P., Capone, J. P. (2002). Host Cell Factor-1 Interacts with and Antagonizes Transactivation by the Cell Cycle Regulatory Factor Miz-1. J. Biol. Chem. 277: 46799-46808 [Abstract] [Full Text]  
  • Lee, S., Herr, W. (2001). Stabilization but Not the Transcriptional Activity of Herpes Simplex Virus VP16-Induced Complexes Is Evolutionarily Conserved among HCF Family Members. J. Virol. 75: 12402-12411 [Abstract] [Full Text]  
  • Luciano, R. L., Wilson, A. C. (2000). N-terminal transcriptional activation domain of LZIP comprises two LxxLL motifs and the Host Cell Factor-1 binding motif. Proc. Natl. Acad. Sci. USA 10.1073/pnas.190062797v1 [Abstract] [Full Text]  
  • Vogel, J. L., Kristie, T. M. (2000). Autocatalytic proteolysis of the transcription factor-coactivator C1 (HCF): A potential role for proteolytic regulation of coactivator function. Proc. Natl. Acad. Sci. USA 10.1073/pnas.160266697v1 [Abstract] [Full Text]  
  • Zhou, H.-J., Wong, C.-M., Chen, J.-H., Qiang, B.-Q., Yuan, J.-G., Jin, D.-Y. (2001). Inhibition of LZIP-mediated Transcription through Direct Interaction with a Novel Host Cell Factor-like Protein. J. Biol. Chem. 276: 28933-28938 [Abstract] [Full Text]  
  • Vogel, J. L., Kristie, T. M. (2000). Autocatalytic proteolysis of the transcription factor-coactivator C1 (HCF): A potential role for proteolytic regulation of coactivator function. Proc. Natl. Acad. Sci. USA 97: 9425-9430 [Abstract] [Full Text]  
  • Luciano, R. L., Wilson, A. C. (2000). N-terminal transcriptional activation domain of LZIP comprises two LxxLL motifs and the Host Cell Factor-1 binding motif. Proc. Natl. Acad. Sci. USA 97: 10757-10762 [Abstract] [Full Text]