The mTOR chromatin-bound interactome in prostate cancer
Catherine R. Dufour,
Charlotte Scholtes,
Ming Yan,
Yonghong Chen,
Lingwei Han,
Ting Li,
Hui Xia,
Qiyun Deng,
Mathieu Vernier,
Vincent Giguère
Affiliations
Catherine R. Dufour
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada
Charlotte Scholtes
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada
Ming Yan
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada
Yonghong Chen
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada; Department of Biochemistry, Faculty of Medicine, McGill University, Montréal, QC H3G 1Y6, Canada
Lingwei Han
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada; Department of Biochemistry, Faculty of Medicine, McGill University, Montréal, QC H3G 1Y6, Canada
Ting Li
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada
Hui Xia
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada; Department of Biochemistry, Faculty of Medicine, McGill University, Montréal, QC H3G 1Y6, Canada
Qiyun Deng
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada; Department of Biochemistry, Faculty of Medicine, McGill University, Montréal, QC H3G 1Y6, Canada
Mathieu Vernier
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada
Vincent Giguère
Rosalind and Morris Goodman Cancer Institute, McGill University, Montréal, QC H3A 1A3, Canada; Department of Biochemistry, Faculty of Medicine, McGill University, Montréal, QC H3G 1Y6, Canada; Corresponding author
Summary: A growing number of studies support a direct role for nuclear mTOR in gene regulation and chromatin structure. Still, the scarcity of known chromatin-bound mTOR partners limits our understanding of how nuclear mTOR controls transcription. Herein, comprehensive mapping of the mTOR chromatin-bound interactome in both androgen-dependent and -independent cellular models of prostate cancer (PCa) identifies a conserved 67-protein interaction network enriched for chromatin modifiers, transcription factors, and SUMOylation machinery. SUMO2/3 and nuclear pore protein NUP210 are among the strongest interactors, while the androgen receptor (AR) is the dominant androgen-inducible mTOR partner. Further investigation reveals that NUP210 facilitates mTOR nuclear trafficking, that mTOR and AR form a functional transcriptional module with the nucleosome remodeling and deacetylase (NuRD) complex, and that androgens specify mTOR-SUMO2/3 promoter-enhancer association. This work identifies a vast network of mTOR-associated nuclear complexes advocating innovative molecular strategies to modulate mTOR-dependent gene regulation with conceivable implications for PCa and other diseases.
