Interaction of HCF-1 with a cellular nuclear export factor.
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.
Mahajan
Shahana S
SS
Department of Microbiology and the Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
Little
Markus M
MM
Vazquez
Rafael
R
Wilson
Angus C
AC
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D049452:Green Fluorescent Proteins; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D051863:Host Cell Factor C1; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014157:Transcription Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D018076:DNA, Complementary; C497692:HCFC1 protein, human; C469750:HCFC1R1 protein, human; C497693:Hcfc1 protein, mouse; D017405:Herpes Simplex Virus Protein Vmw65; D051863:Host Cell Factor C1; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D011506:Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D007930:Leucine