May 2010

[MCP] An Estrogen-Actin Network

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Map of the ERa and b-actin interactions identified in hormone-stimulated MCF-7 cells.

Estrogen receptor a is a member of the steroid/nuclear receptor family of transcriptional regulators that, upon estrogen binding, induces a series of genomic and extragenomic effects that regulate many cellular functions. Along the way, ERa interacts with numerous transcriptional co-regulators and other binding partners. Identifying these molecular partners and interactions is required to define the basis of estrogen function, especially in mammary cells where estrogen is a potent tumor inducer. In this study, the researchers used affinity purification to map and characterize the ERa interactome in hormone-responsive human breast cancer cell nuclei. The analysis of purified ERa-containing complexes uncovered a ligand-dependent multiprotein complex comprising b-actin, myosins and several proteins involved in actin filament organization, actin dynamics and actin-mediated transcriptional and translational regulation. These ERa and actin complexes assembled in the nucleus shortly after receptor activation and gene knockdown studies showed that gelsolin and the nuclear isoform of myosin 1c are key determinants for complex assembly and/or stability. This work suggests that the actin network plays a role in ERa nuclear activity in breast cancer cells, including coordinating target gene activity, reorganizing chromatin and promoting ribosome biogenesis. 

Identification of a Hormone-regulated Dynamic Nuclear Actin Network Associated with Estrogen Receptor a in Human Breast Cancer Cell Nuclei 

Concetta Ambrosino, Roberta Tarallo, Angela Bamundo, Danila Cuomo1, Gianluigi Franci, Giovanni Nassa, Ornella Paris, Maria Ravo, Alfonso Giovane, Nicola Zambrano, Tatiana Lepikhova, Olli A. Jänne, Marc Baumann, Tuula A. Nyman, Luigi Cicatiello and Alessandro Weisz

Mol. Cell. Proteomics, published online March 22, 2010

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