Allosteric activation of acid alpha-glucosidase by the human papillomavirus E7 protein

Changes in the cellular carbohydrate metabolism are a hallmark of malignant transformation and represent one of the earliest discernible events in tum origenesis. In the early stages of certain epithelial cancers, a metabolic switch is regularly observed, in which slowly growing glycogenotic cells ar e converted to highly proliferating basophilic cells. This step is accompan ied by a rapid depletion of the intracellular glycogen stores, which in liv er carcinogenesis results from the activation of the enzyme acid alpha-gluc osidase by an as yet unknown mechanism. We show here that acid alpha-glucos idase is a target for the E7 protein encoded by human papillomavirus type 1 6, a human tumor virus that plays a key role in the genesis of cervical car cinoma. We show that expression of E7 induces the catalytic activity of aci d alpha-glucosidase in vivo and wild type E7, but not ransformation-deficie nt mutants bind directly to acid cu-glucosidase and increase the catalytic activity of the enzyme in vitro. The data suggest that the E7 protein encod ed by human papillomavirus type 16 can act as an allosteric activator of ac id alpha-glucosidase.