We propose that PR acts as a sensor for activated mitogenic protein kinases (that is, MAPKs and CDK2) frequently elevated in human breast cancer; under the influence of elevated Ser294 phosphorylation, genes that are sensitive to (that is, normally repressed by) PR SUMOylation may instead cooperate to drive breast cancer cell proliferation and pro-survival signaling. The gene discussed is CDK2; the disease is breast cancer.