Search Results
You are looking at 1 - 1 of 1 items for
- Author: Katherine S Bridge x
- Refine by access: All content x
Search for other papers by Weiye Zhao in
Google Scholar
PubMed
Search for other papers by Susanna F Rose in
Google Scholar
PubMed
Search for other papers by Ryan Blake in
Google Scholar
PubMed
Search for other papers by Aňze Godicelj in
Google Scholar
PubMed
Search for other papers by Amy E Cullen in
Google Scholar
PubMed
Search for other papers by Jack Stenning in
Google Scholar
PubMed
Search for other papers by Lucy Beevors in
Google Scholar
PubMed
Search for other papers by Marcel Gehrung in
Google Scholar
PubMed
Search for other papers by Sanjeev Kumar in
Google Scholar
PubMed
Search for other papers by Kamal Kishore in
Google Scholar
PubMed
Search for other papers by Ashley Sawle in
Google Scholar
PubMed
Search for other papers by Matthew Eldridge in
Google Scholar
PubMed
Search for other papers by Federico M Giorgi in
Google Scholar
PubMed
York Biomedical Research Institute, University of York, York, UK
Search for other papers by Katherine S Bridge in
Google Scholar
PubMed
Search for other papers by Florian Markowetz in
Google Scholar
PubMed
York Biomedical Research Institute, University of York, York, UK
The Alan Turing Institute, Kings Cross, London, UK
Search for other papers by Andrew N Holding in
Google Scholar
PubMed
The estrogen receptor-α (ER) drives 75% of breast cancers. On activation, the ER recruits and assembles a 1–2 MDa transcriptionally active complex. These complexes can modulate tumour growth, and understanding the roles of individual proteins within these complexes can help identify new therapeutic targets. Here, we present the discovery of ER and ZMIZ1 within the same multi-protein assembly by quantitative proteomics, and validated by proximity ligation assay. We characterise ZMIZ1 function by demonstrating a significant decrease in the proliferation of ER-positive cancer cell lines. To establish a role for the ER-ZMIZ1 interaction, we measured the transcriptional changes in the estrogen response post-ZMIZ1 knockdown using an RNA-seq time-course over 24 h. Gene set enrichment analysis of the ZMIZ1-knockdown data identified a specific delay in the response of estradiol-induced cell cycle genes. Integration of ENCODE data with our RNA-seq results identified that ER and ZMIZ1 both bind the promoter of E2F2. We therefore propose that ER and ZMIZ1 interact to enable the efficient estrogenic response at subset of cell cycle genes via a novel ZMIZ1–ER–E2F2 signalling axis. Finally, we show that high ZMIZ1 expression is predictive of worse patient outcome, ER and ZMIZ1 are co-expressed in breast cancer patients in TCGA and METABRIC, and the proteins are co-localised within the nuclei of tumour cell in patient biopsies. In conclusion, we establish that ZMIZ1 is a regulator of the estrogenic cell cycle response and provide evidence of the biological importance of the ER–ZMIZ1 interaction in ER-positive patient tumours, supporting potential clinical relevance.