THE HCF REPEAT IS AN UNUSUAL PROTEOLYTIC CLEAVAGE SIGNAL

The herpes simplex virus VP16-associated protein HCF is a nuclear host -cell factor that exists as a family of polypeptides encoded by a sing le gene. The mature HCF polypeptides are amino- and carboxy-terminal f ragments of a large similar to 300-kD precursor protein that arise thr ough cleavage at one or more centrally located sites. The sites of cle avage are the HCE repeats, highly conserved 26-amino-acid sequences re peated six times in the HCF precursor protein. The BCE repeat alone is sufficient to induce cleavage of a heterologous protein, and cleavage occurs at a defined site-PPCE/THET-within the HCF repeat. Alanine-sca n mutagenesis was used to identify a large 18-amino-acid segment of th e HCE repeat that is important to induce cleavage of a heterologous pr otein. Even though HCF is cleaved, the majority of amino- and carboxy- terminal cleavage products remain tightly, albeit noncovalently, assoc iated. Modulation of this noncovalent association may provide a mechan ism for regulating HCF activity. For example, the cleaved products of an alternative mRNA splicing variant of HCF do not remain associated.