The mTOR chromatin-bound interactome in prostate cancer

Area of Science:

• Molecular Biology
• Cell Biology
• Cancer Research

Background:

• Nuclear mammalian target of rapamycin (mTOR) plays a role in gene regulation and chromatin structure.
• Understanding how nuclear mTOR controls transcription is limited by the scarcity of known chromatin-bound mTOR partners.

Purpose of the Study:

• To comprehensively map the mTOR chromatin-bound interactome in prostate cancer (PCa) models.
• To identify novel nuclear mTOR partners and elucidate their role in transcriptional regulation.

Main Methods:

• Chromatin immunoprecipitation followed by mass spectrometry (ChIP-MS) to identify mTOR interactors.
• Androgen-dependent and -independent PCa cellular models were used.
• Functional assays to investigate the roles of identified interactors (e.g., NUP210, AR, SUMO2/3).

Main Results:

• A conserved 67-protein network interacting with chromatin-bound mTOR was identified.
• Key interactors include SUMO2/3, nuclear pore protein NUP210, and the androgen receptor (AR).
• NUP210 facilitates mTOR nuclear import; mTOR, AR, and the NuRD complex form a transcriptional module; androgens regulate mTOR-SUMO2/3 association with DNA elements.

Conclusions:

• This study identifies a large network of nuclear mTOR-associated complexes in PCa.
• Findings provide insights into mTOR-dependent gene regulation and suggest novel therapeutic strategies for PCa and other diseases.