The Tuberous Sclerosis 2 Gene Product Can Localize to Nuclei in a Phosphorylation-Dependent Manner

The tuberous sclerosis 2 (TSC2) gene has been genetically mapped to a disease characterized by abnormal cell proliferation that results in the production of tumorous lesions in a variety of tissues. The molecular mechanism for TSC2 mediation of tuberous sclerosis is unclear but it appears to be related to its ability to cytoplasmically interact with a second gene, TSC1, mapping to the disease. These proteins are linked to constraints on cell cycle signaling pathways and therefore envisioned to function as tumor suppressor genes. In previous studies we have demonstrated TSC2 associations with steroid receptor family members and modulation of their gene expression capabilities. Here we provide evidence for TSC2 translocation to the nucleus and a possible role for phosphorylation in both TSC2 translocation and TSC2 modulation of steroid receptor-mediated transcription.