A protein sequestering system reveals control of cellular programs by the transcriptional coactivator HCF-1.
The mammalian transcriptional coactivator HCF-1 is a critical component of the multiprotein herpes simplex virus immediate early gene enhancer core complex. The protein has also been implicated in basic cellular processes such as cell-cycle progression, transcriptional coactivation, and mRNA processing. Functions have been attributed to HCF-1 primarily from analyses of protein-protein interactions and from the cell-cycle-arrested phenotype of an HCF-1 temperature-sensitive mutant. However, neither the mechanisms involved nor specific cellular transcriptional targets have been identified. As the protein is essential for cell viability and proliferation, a genetic system was developed to specifically sequester the nuclear factor in the cell cytoplasm in a regulated manner. This approach exhibits no significant cell toxicity yet clearly demonstrates the requirement of available nuclear HCF-1 for herpes simplex virus immediate early gene expression during productive infection. Additionally, cellular transcriptional events were identified that contribute to understanding the functions ascribed to the protein and implicate the protein in events that impact the regulation of critical cellular processes.
Khurana
Bharat
B
Laboratory of Viral Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kristie
Thomas M
TM
D000199:Actins / Q000235:genetics; D000595:Amino Acid Sequence; D001665:Binding Sites; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002468:Cell Physiological Phenomena; D002470:Cell Survival; D002477:Cells / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D003593:Cytoplasm / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000235:genetics*; D006367:HeLa Cells; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D051863:Host Cell Factor C1; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011993:Recombinant Fusion Proteins; D013696:Temperature; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication
D000199:Actins; C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D014764:Viral Proteins