# Construction of the Androgen Receptor Interactome: A Molecular Framework for Probing Genetic Interactions in Androgen-Dependent Signaling

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2022 · $391,682

## Abstract

Androgen receptor is a powerful sex-steroid hormone receptor that mediates homeostatic and pathological
functions in hormone-responsive systems in humans. Over the past 30 years, since the original cloning of the
androgen receptor cDNA, molecular insights into androgen receptor function, both normal and pathological,
have been gleaned from the discovery of proteins that bind and regulate androgen receptor activity. These
androgen receptor-interacting proteins, better known as the AR-interactome, constitute a functionally diverse
spectrum of proteins that modulate androgen receptor function in space and time at the cellular level. Like
other sex-steroid hormone receptor family members, androgen receptor is a very sticky receptor. It has more
than 350 binding partners, which allows androgen receptor to serve as a hub to regulate cellular signaling at
the molecular level through dynamic protein interactions with the AR-interactome. Unfortunately, the AR-
interactome continues to grow over time with no clear end in sight. Our inability to define the AR-interactome in
a single cellular model has made it nearly impossible to experimentally replicate the AR-interactome and
understand how their coordinated actions regulate AR-dependent signaling in space and time. Thus,
quantitative and predictive models of AR-dependent signaling remain speculative at best. Our scientific
premise is that the careful annotation and discovery of the AR-interactome in cells will lay the foundation for
understanding how this subproteome contributes to physiologic and pathologic androgen receptor functions in
hormone-responsive systems. Thus, we have proposed an experimental plan to annotate the AR-interactome
in androgen-sensitive cellular models using cutting-edge, quantitative proteomic techniques. Our proteomic
approaches will define a spatiotemporal map of the AR-interactome in cells, and lay the foundation for probing
genetic relationships within and between protein complexes comprising the AR-interactome. The proteomic
findings will allow us to develop testable models of AR-dependent signaling in cellular systems. These models
will provide a molecular framework to understand how androgen-mediated signaling operates under
homeostatic and pathological states. More importantly, they will guide the discovery of novel druggable targets
among the AR-interactome so that corrupted AR-dependent signaling can be attenuated in androgen receptor-
related pathologies that afflict reproductive and non-reproductive systems in humans.

## Key facts

- **NIH application ID:** 10455000
- **Project number:** 5R01GM143399-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Michael E Wright
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $391,682
- **Award type:** 5
- **Project period:** 2021-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455000

## Citation

> US National Institutes of Health, RePORTER application 10455000, Construction of the Androgen Receptor Interactome: A Molecular Framework for Probing Genetic Interactions in Androgen-Dependent Signaling (5R01GM143399-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10455000. Licensed CC0.

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