Elucidation of the BMI1 interactome identifies novel regulatory roles in glioblastoma

Author:

Freire-Benéitez Verónica1,Pomella Nicola1,Millner Thomas O1,Dumas Anaëlle A1,Niklison-Chirou Maria Victoria12,Maniati Eleni3ORCID,Wang Jun3ORCID,Rajeeve Vinothini3ORCID,Cutillas Pedro3,Marino Silvia1ORCID

Affiliation:

1. Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, E1 2AT, London, UK

2. Centre for Therapeutic Innovation (CTI-Bath), Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK

3. Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6AS UK

Abstract

Abstract Glioblastoma (GBM) is the most common and aggressive intrinsic brain tumour in adults. Epigenetic mechanisms controlling normal brain development are often dysregulated in GBM. Among these, BMI1, a structural component of the Polycomb Repressive Complex 1 (PRC1), which promotes the H2AK119ub catalytic activity of Ring1B, is upregulated in GBM and its tumorigenic role has been shown in vitro and in vivo. Here, we have used protein and chromatin immunoprecipitation followed by mass spectrometry (MS) analysis to elucidate the protein composition of PRC1 in GBM and transcriptional silencing of defining interactors in primary patient-derived GIC lines to assess their functional impact on GBM biology. We identify novel regulatory functions in mRNA splicing and cholesterol transport which could represent novel targetable mechanisms in GBM.

Funder

Brain Tumour Research

Barts Charity

Brain Tumour Charity

The Medical College of Saint Bartholomew's Hospital Trust

NIHR

Cancer Research UK

Publisher

Oxford University Press (OUP)

Subject

General Medicine

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