Stimulation by lithium of the interaction between the transcription factor CREB and its co-activator TORC

Bioscience Reports
Annette HeinrichWillhart Knepel

Abstract

Lithium salts are clinically important drugs used to treat bipolar mood disorder. The mechanisms accounting for the clinical efficacy are not completely understood. Chronic treatment with lithium is required to establish mood stabilization, suggesting the involvement of neuronal plasticity processes. CREB (cAMP-response-element-binding protein) is a transcription factor known to mediate neuronal adaptation. Recently, the CREB-co-activator TORC (transducer of regulated CREB) has been identified as a novel target of lithium and shown to confer an enhancement of cAMP-induced CREB-directed gene transcription by lithium. TORC is sequestered in the cytoplasm and its nuclear translocation controls CREB activity. In the present study, the effect of lithium on TORC function was investigated. Lithium affected neither the nuclear translocation of TORC nor TORC1 transcriptional activity, but increased the promoter occupancy by TORC1 as revealed by chromatin immunoprecipitation assay. In a mammalian two-hybrid assay, as well as in a cell-free GST (glutathione transferase) pull-down assay, lithium enhanced the CREB-TORC1 interaction. Magnesium ions strongly inhibited the interaction between GST-CREB and TORC1 and this effect was reversed by ...Continue Reading

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Citations

Jan 22, 2013·The International Journal of Neuropsychopharmacology·Seong S ShimRonald F Mervis
Nov 22, 2019·Frontiers in Oncology·Shilpa ThakurJoanna Klubo-Gwiezdzinska
Sep 9, 2017·Metallomics : Integrated Biometal Science·Magali Roux, Anthony Dosseto

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