BRCA1 IS SECRETED AND EXHIBITS PROPERTIES OF A GRANIN

Germline mutations in BRCA1 are responsible for most cases of inherite d breast and ovarian cancer. However, the function of the BRCA1 protei n has remained elusive. We now show that BRCA1 encodes a 190-kD protei n with sequence homology and biochemical analogy to the granin protein family. Interestingly, BRCA2 also includes a motif similar to the gra nin consensus at the C terminus of the protein. Both BRCA1 and the gra nins localize to secretory vesicles, are secreted by a regulated pathw ay, are posttranslationally glycosylated and are responsive to hormone s. As a regulated secretory protein, BRCA1 appears to function by a me chanism not previously described for tumour suppressor gene products.