HPIP is a small cellular polypeptide that binds to the beta-propeller domain of HCF-1. HPIP regulates HCF-1 activity by modulating its subcellular localization. HCF-1 is a cellular protein required by VP16 to activate the herpes simplex virus- 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. HPIP-mediated export may provide the pool of cytoplasmic HCF-1 required for import of virion-derived VP16 into the nucleus.