Abstract
The nuclear receptor estrogen receptor 2 (ESR2, ERβ) modulates cancer cell proliferation and tumor growth, exerting an oncosuppressive role in breast cancer (BC). Interaction proteomics by tandem affinity purification coupled to mass spectrometry was previously applied in BC cells to identify proteins acting in concert with ERβ to control key cellular functions, including gene transcription, RNA splicing and post-transcriptional mRNA regulation. These studies revealed an involvement of RNA in ERβ interactome assembly and functions. By applying native protein complex purification followed by nano LC-MS/MS before and after in vitro RNA removal, we generated a large dataset of newly identified nuclear ERβ interactors, including a subset associating with the receptor via RNA bridging. These datasets will be useful to investigate further the role of ERβ, nuclear RNAs and the other proteins identified here in BC and other cell types.
Highlights
Background & SummaryThe role of estrogen receptor β (ERβ) in cancer biology is still an open issue, despite its potential use as biomarker and drug target
Some of the results obtained in clinical samples have been challenged, due to the existence of multiple isoform of this protein and uncertainties concerning the specificity of the available antibodies for its detection in tissue specimens, all these evidences points to a key role of ERβ in breast cancer (BC) biology
We recently demonstrated that ERβ can interact with AGO2 in BC cells and that this is mediated by one or more RNAs19, suggesting for the first time that RNA plays a role in assembly and/or stabilization of ERβ interactomes, as already shown for other nuclear receptors[20,21,22]
Summary
The role of estrogen receptor β (ERβ) in cancer biology is still an open issue, despite its potential use as biomarker and drug target. ERβ-containing nuclear protein complexes, purified by affinity chromatography (tandem affinity purification (TAP), partial procedure)[23], were analysed by nano LC-MS/MS, leading to the identification of the largest receptor interactome mapped so far, comprising 1897 specific components, following exclusion of contaminants identified in control samples from ERβ-negative MCF-7 cells processed in the same way, excluding potential contaminants identified in Ct-ERβ samples (e.g. Keratins and Immunoglobulins) (Data Citation 1: ‘Identified proteins’ table) This ERβ interacting network comprises several sub-networks, comprising proteins involved in cellular functions known to be controlled by this receptor, including transcription, cell death and apoptosis and RNA splicing (Fig. 2). The dataset presented here will be useful to investigate the molecular mechanism of ERβ activity and to design ways to investigate composition and functional roles of macromolecular complexes in BC cell nuclei comprising proteins and RNAs, aiming at the identification of interactome nodes representing potential drug targets against this, and possibly other, cancers
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