HCF-1 amino- and carboxy-terminal subunit association through two separatesets of interaction modules: Involvement of fibronectin type 3 repeats

When herpes simplex virus infects permissive cells, the viral regulatory pr otein VP16 forms a specific complex with HCF-1, a preexisting nuclear prote in involved in cell proliferation. The majority of HCF-1 in the cell is a c omplex of associated amino (BCF-1(N))- and carboxy (HCF-1(C))-terminal subu nits that result from an unusual proteolytic processing of a large precurso r polypeptide. Here, we have characterized the structure and function of se quences required for HCF-1(N) and HCF-1(C) subunit association. HCF-1 conta ins two matched pairs of self-association sequences called SAS1 and SAS2. O ne of these matched association sequences, SAS1, consists of a short 43-ami no-acid region of the HCF-1(N) subunit, which associates with a carboxy-ter minal region of the HCF-1(C) subunit that is composed of a tandem pair of f ibronectin type 3 repeats, a structural motif known to promote protein-prot ein interactions. Unexpectedly, the related protein HCF-2, which is not pro teolyzed, also contains a functional SAS1 association element, suggesting t hat this element does not function solely to maintain HCF-1(N) and HCF-1(C) subunit association. HCF-1(N) subunits do not possess a nuclear localizati on signal. We show that, owing to a carboxy-terminal HCF-1 nuclear localiza tion signal, HCF-1(C) subunits can recruit HCF-1(N) subunits to the nucleus .