CREB binding protein (CBP) is a transcriptional cofactor with intrinsic histone acetyl transferase activity (HAT). We have observed that CBP interacts with BRCA2 and mediates post-translational glycosylation of BRCA2. The binding of CBP to the amino-terminal region of BRCA2 is necessary for the glycosylation at residue 272 of BRCA2. Digestion with peptide N-glycosidase F indicates that the glycosylation of BRCA2 is N-linked. It is possible that this novel CBP-mediated post-translational N-glycosylation activity alters the conformation of CBP-interacting proteins, leading to regulation of gene expression, cell growth and differentiation.