VP16 targets an amino-terminal domain of HCF involved in cell cycle progression

Wilson, A. C., Freiman, R. N., Goto, H., Nishimoto, T., Herr, W. (October 1997) VP16 targets an amino-terminal domain of HCF involved in cell cycle progression. Molecular and Cellular Biology, 17 (10). pp. 6139-46. ISSN 0270-7306

URL: http://www.ncbi.nlm.nih.gov/pubmed/9315674

Abstract

The herpes simplex virus (HSV) regulatory protein VP16 activates HSV immediate-early gene transcription through formation of a multiprotein-DNA complex on viral promoters that includes the preexisting nuclear proteins HCF and Oct-1. The HCF protein is a complex of amino- and carboxy-terminal polypeptides derived from a large (approximately 2,000-amino-acid) precursor by proteolytic processing. Here we show that a 361-residue amino-terminal region of HCF is sufficient to bind VP16, stabilize VP16-induced complex assembly with Oct-1 and DNA, and activate transcription in vivo. This VP16 interaction region contains six kelch-like repeats, a degenerate repeat motif that is likely to fold as a distinctive beta-propeller structure. The third HCF kelch repeat includes a proline residue (P134) that is mutated to serine in hamster tsBN67 cells, resulting in a temperature-sensitive defect in cell proliferation. This missense mutation also prevents direct association between HCF and VP16, suggesting that VP16 mimics a cellular factor required for cell proliferation. Rescue of the tsBN67 cell proliferation defect by HCF, however, requires both the VP16 interaction domain and an adjacent basic region, indicating that HCF utilizes multiple regions to promote cell cycle progression.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Animals Cell Cycle/ physiology Cell Line Cricetinae Epithelium Gene Expression Regulation, Viral/physiology Herpes Simplex Virus Protein Vmw65/ metabolism Host Cell Factor C1 Humans Kidney/cytology Molecular Sequence Data Point Mutation Protein Binding Proteins/chemistry/genetics/ metabolism Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Saccharomyces cerevisiae/genetics Simplexvirus/genetics Temperature Trans-Activation (Genetics)/physiology Transcription Factors Transfection
Subjects: organism description > yeast > Saccharomyces
organs, tissues, organelles, cell types and functions > tissues types and functions > epithelium
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
organism description > virus > herpes simplex virus
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
organism description > virus > viral transfection
CSHL Authors:
Communities: CSHL labs > Herr lab
Depositing User: Kathleen Darby
Date: October 1997
Date Deposited: 07 May 2014 16:02
Last Modified: 07 May 2014 16:02
PMCID: PMC232464
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30013

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