BRCA1 is secreted and exhibits properties of a granin.
Germline mutations in BRCA1 are responsible for most cases of inherited breast and ovarian cancer. However, the function of the BRCA1 protein has remained elusive. We now show that BRCA1 encodes a 190-kD protein with sequence homology and biochemical analogy to the granin protein family. Interestingly, BRCA2 also includes a motif similar to the granin consensus at the C terminus of the protein. Both BRCA1 and the granins localize to secretory vesicles, are secreted by a regulated pathway, are post-translationally glycosylated and are responsive to hormones. As a regulated secretory protein, BRCA1 appears to function by a mechanism not previously described for tumour suppressor gene products.
Jensen
R A
RA
Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-5310, USA.
Thompson
M E
ME
Jetton
T L
TL
Szabo
C I
CI
van der Meer
R
R
Helou
B
B
Tronick
S R
SR
Page
D L
DL
King
M C
MC
Holt
J T
JT
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics*; D011506:Proteins / Q000737:chemistry; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D014157:Transcription Factors