The Prostate Cancer mTOR Chromatin-Bound Interactome

ABSTRACT: Growing 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, we comprehensively mapped the mTOR chromatin-bound interactome in four cellular models of prostate cancer (PCa) identifying a conserved 67-protein interaction network enriched for epigenetic and transcription factors as well as SUMOylation machinery in both androgen-dependent and -independent cells. Notably, 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 showed that NUP210 facilitates mTOR nuclear trafficking, that mTOR, AR and NuRD act as a functional transcriptional complex, and that androgens dictate mTOR-SUMO2/3 promoter-enhancer specificity. This work identifies a vast network of mTOR-associated nuclear complexes advocating novel molecular strategies to modulate mTOR-dependent gene regulation with evident implications for PCa and other diseases.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Prostate Epithelium Cell Line, Prostate Cancer Cell Line, Cell Line Cell

DISEASE(S): Prostate Adenocarcinoma,Prostate Carcinoma

SUBMITTER: Vincent Giguere  

LAB HEAD: Vincent Giguere

PROVIDER: PXD026101 | Pride | 2022-04-01

REPOSITORIES: Pride