| Added by | mollevi |
|---|---|
| Last modified by | Cavailles |
| Group name | EquipeVC |
| Item Type | Journal Article |
| Title | Transcriptional repression of estrogen receptor alpha signaling by SENP2 in breast cancer cells |
| Creator | Nait Achour et al. |
| Author | T. Nait Achour |
| Author | S. Sentis |
| Author | C. Teyssier |
| Author | A. Philippat |
| Author | A. Lucas |
| Author | L. Corbo |
| Author | V. Cavailles |
| Author | S. Jalaguier |
| Abstract | Estrogen receptors (ERs) are ligand-activated transcription factors involved in many physiological and pathological processes, including breast cancer. Their activity is fine-tuned by posttranslational modifications, notably sumoylation. In the present study, we investigated the role of the small ubiquitin-related modifier (SUMO) protease, SUMO1/sentrin/suppressor of Mif 2-specific peptidase 2 (SENP2), in the regulation of ERalpha activity. We first found SENP2 to significantly repress estradiol-induced transcriptional activity in breast cancer cells (MCF7 and T47D). This effect was observed with a reporter plasmid and on endogenous genes such as TFF1 and CTSD, which were shown to recruit SENP2 in chromatin immunoprecipitation experiments. Using glutathione S-transferase pull-down, coimmunoprecipitation and proximity ligation assays, SENP2 was found to interact with ERalpha and this interaction to be mediated by the amino-terminal region of the protease and the hinge region of the receptor. Interestingly, we demonstrated that ERalpha repression by SENP2 is independent of its SUMO protease activity and requires a transcriptional repressive domain located in the amino-terminal end of the protease. Using small interfering RNA assays, we evidenced that this domain recruits the histone deacetylase 3 (HDAC3), to be fully active. Furthermore, using both overexpression and knockdown strategies, we showed that SENP2 robustly represses estrogen-dependent and independent proliferation of MCF7 cells. We provided evidence that this effect requires both the proteolytic and transcriptional activities of SENP2. Altogether, our study unravels a new property for a SUMO protease and identifies SENP2 as a classical transcription coregulator. |
| Publication | Mol Endocrinol |
| Volume | 28 |
| Pages | 183-96 |
| Date | Feb 2014 |
| Journal Abbr | Molecular endocrinology |
| DOI | 10.1210/me.2013-1376 |
| ISSN | 1944-9917 (Electronic) 0888-8809 (Linking) |
| Tags | *Gene Expression Regulation, Neoplastic, *Gene Silencing, Breast Neoplasms, Cell Proliferation, Cysteine Endopeptidases/*physiology, Estradiol/physiology, Estrogen Receptor alpha/*physiology, Female, Histone Deacetylases/metabolism, Humans, MCF-7 Cells, original, own, Promoter Regions, Genetic, Protein Binding, Protein Structure, Tertiary, Transcription, Genetic |
| Date Added | 2018/11/14 - 12:10:52 |
| Date Modified | 2019/05/17 - 11:58:28 |
| Notes and Attachments | (Note) (Note) 24422630 (Attachment) |
Institut de Recherche en Cancérologie de
