| First Author | Kanaujiya JK | Year | 2013 |
| Journal | Proteomics | Volume | 13 |
| Issue | 14 | Pages | 2100-12 |
| PubMed ID | 23576398 | Mgi Jnum | J:201457 |
| Mgi Id | MGI:5514125 | Doi | 10.1002/pmic.201200534 |
| Citation | Kanaujiya JK, et al. (2013) Proteomic identification of Profilin1 as a corepressor of estrogen receptor alpha in MCF7 breast cancer cells. Proteomics 13(14):2100-12 |
| abstractText | Nuclear receptor coregulators play an important role in the transcriptional regulation of nuclear receptors. In the present study, we aimed to identify estrogen receptor alpha (ERalpha) interacting proteins in Tamoxifen treated MCF7 cells. Using in vitro GST-pull down assay with ERalpha ligand-binding domain (ERalpha-LBD) and MS-based proteomics approach we identified Profilin1 as a novel ERalpha interacting protein. Profilin1 contains I/LXX/L/H/I amino acid signature motif required for corepressor interaction with ERalpha. We show that these two proteins physically interact with each other both in vitro as well as in vivo by GST-pull down and coimmunoprecipitation, respectively. We further show that these two proteins also colocalize together in the nucleus. Previous studies have reported reduced expression of Profilin1 in breast cancer; and here we found that Tamoxifen increases Profilin1 expression in MCF7 cells. Our data demonstrate that over expression of Profilin1 inhibits ERalpha-mediated transcriptional activation as well as its downstream target genes in ERalpha positive breast cancer cells MCF7. In addition, Profilin1 overexpression in MCF7 cells leads to inhibition of cell proliferation that apparently is due to enhanced apoptosis. In nutshell, these data indicate that MS-based proteomics approach identifies a novel ERalpha interacting protein Profilin1 that serves as a putative corepressor of ERalpha functions. |
