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bioRxiv · 10.64898/2026.08.03.742469

A Spatiotemporal Atlas of Extranuclear Androgen Receptor Proximal Interaction Networks

Ptak, C. C.·O'Rourke, C.·Eng, J.·Radoshevich, L.·Wright, M. E.
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Abstract

Androgen receptor-interacting proteins (AR-IPs) number close to 1,000, yet their organization across subcellular space and time remains uncharted. Proximity labeling identifies direct partners and neighboring proteins, thereby expanding AR-IPs to AR-proximal interacting proteins (AR-PIPs). Using proximity labeling quantitative mass spectrometry (PL-qMS), we construct a spatiotemporal atlas of the cytosolic, microsomal, and nuclear compartments in LNCaP prostate tumor cells. PL-qMS recovered 82.2% of the known AR-interactome in extranuclear compartments and 84.2% in the nucleus, identifying 4,751 AR-PIPs that remodel across an androgen time course. The retromer formed an androgen-sensitive AR-proximal interaction network (AR-PIN) verified by proximity ligation assays (PLAs). Moreover, partial VPS26A disruption attenuated androgen-regulated transcription and mislocalized the AR coactivator TMF1, defining a retromer-AR-TMF1 axis. In the nucleus, AR-PINs recover 100% of the Launonen 2021 ChIP-SICAP chromatome and reveal a PLA-verified translation-to-transcription handoff involving eIF4G and 4E-BP1. This spatiotemporal atlas provides a proximal framework for probing AR function in cells.

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Ptak, C. C., O'Rourke, C., Eng, J., Radoshevich, L., Wright, M. E.. 2026-08-06. A Spatiotemporal Atlas of Extranuclear Androgen Receptor Proximal Interaction Networks. https://doi.org/10.64898/2026.08.03.742469

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