A Temporal Atlas of the Nuclear Androgen Receptor Proximal Interactome

Androgen receptor-interacting proteins (AR-IPs) comprise nearly 1,000 cataloged partners, yet how AR engages this interactome inside the nucleus, in what temporal order, and through what molecular handoffs, remains uncharted. Here, we construct a minute-scale temporal atlas of the nuclear AR proximal interactome by proximity-labeling quantitative mass spectrometry (PL-qMS) in androgen-treated LNCaP prostate cancer cells, capturing 84.2% of the known AR-interactome and resolving 3,378 nuclear AR-proximal interacting proteins (AR-PIPs) across six time points. The atlas recapitulates the cyclic sequential recruitment model established at AR-regulated loci by classical ChIP and recovers 100% of previously known AR interactors from the Launonen 2021 ChIP-SICAP chromatome. Embedded within this canonical chromatin signature, we uncover a time-resolved translation-to-transcription handoff in which cap-binding eIF4G and 4E-BP1 are transiently AR-proximal at the earliest time points, verified by PLA. The atlas converts the AR coregulator catalog into a temporally resolved quantitative framework for AR-dependent transcription. SynopsisA minute-scale temporal atlas of the nuclear AR-proximal interactome resolves a translation-to-transcription handoff during the androgen response. O_LITemporal nuclear AR-proximal interactome atlas in androgen-treated LNCaP cells C_LIO_LI3,378 nuclear AR-PIPs recovered, 100% of previously known Launonen AR partners C_LIO_LICap-binding eIF4G and 4E-BP1 are transiently AR-proximal at early time points C_LIO_LIPLA verifies AR-eIF4G and AR-4E-BP1 proximal interactions pointing to a translation-to-transcription handoff C_LI