A central role for the metabolic sensor CtBP in controlling the expression of the tumour suppressor BRCA1, in response to oestrogen and the ratio of particular metabolites, is revealed in Nature Structural & Molecular Biology. CtBP1’s control of BRCA1 may help to explain the association between high caloric intake and obesity and increased risk of breast cancer in post-menopausal women.
While BRCA1 mutations are associated with breast cancer, alterations in BRCA1 expression independent of mutations can contribute to sporadic, noninherited forms of the disease. Kevin Gardner and colleagues show that CtBP, involved in repressing gene expression, assembles at the BRCA1 promoter as part of a large complex, where it contributes to turning off BRCA1 expression in response to metabolic status. These findings also indicate that the high levels of CtBP found in some tumours may contribute to malignancies and tumour progression.