Interaction of HCF-1 with a cellular nuclear export factor

J Biol Chem. 2002 Nov 15;277(46):44292-9. doi: 10.1074/jbc.M205440200. Epub 2002 Sep 15.


HCF-1 is a cellular protein required by VP16 to activate the herpes simplex virus (HSV) immediate-early genes. VP16 is a component of the viral tegument and, after release into the cell, binds to HCF-1 and translocates to the nucleus to form a complex with the POU domain protein Oct-1 and a VP16-responsive DNA sequence. This VP16-induced complex boosts transcription of the viral immediate-early genes and initiates lytic replication. In uninfected cells, HCF-1 functions as a coactivator for the cellular transcription factors LZIP and GABP and also plays an essential role in cell proliferation. VP16 and LZIP share a tetrapeptide HCF-binding motif recognized by the beta-propeller domain of HCF-1. Here we describe a new cellular HCF-1 beta-propeller domain binding protein, termed HPIP, which contains a functional HCF-binding motif and a leucine-rich nuclear export sequence. We show that HPIP shuttles between the nucleus and cytoplasm in a CRM1-dependent manner and that overexpression of HPIP leads to accumulation of HCF-1 in the cytoplasm. These data suggest that HPIP regulates HCF-1 activity by modulating its subcellular localization. Furthermore, HPIP-mediated export may provide the pool of cytoplasmic HCF-1 required for import of virion-derived VP16 into the nucleus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus
  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • COS Cells
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Cell Nucleus / metabolism*
  • Cytoplasm / metabolism
  • DNA, Complementary / metabolism
  • Green Fluorescent Proteins
  • Herpes Simplex Virus Protein Vmw65 / metabolism
  • Host Cell Factor C1
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Leucine / metabolism
  • Luminescent Proteins / metabolism
  • Mice
  • Microscopy, Fluorescence
  • Models, Biological
  • Molecular Sequence Data
  • Plasmids / metabolism
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Proteins / metabolism*
  • Rats
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Transcription Factors*
  • Transfection
  • Two-Hybrid System Techniques


  • Carrier Proteins
  • DNA, Complementary
  • HCFC1 protein, human
  • HCFC1R1 protein, human
  • Hcfc1 protein, mouse
  • Herpes Simplex Virus Protein Vmw65
  • Host Cell Factor C1
  • Intracellular Signaling Peptides and Proteins
  • Luminescent Proteins
  • Proteins
  • Transcription Factors
  • Green Fluorescent Proteins
  • Leucine

Associated data

  • GENBANK/AY116892