# Structural mechanisms of FoxM1 regulation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2020 · $272,559

## Abstract

Project Summary
 The goal of this research project is to characterize the molecular mechanisms regulating FoxM1 in
cell proliferation. The FoxM1 transcription factor increases gene expression to drive the cell cycle and
division. FoxM1 expression and activity are high and necessary in many human cancer cells, and thus
FoxM1 is an attractive therapeutic target. We propose and will test a novel structural model for FoxM1
regulation, in which activity is modulated by conformational switching of an intrinsically disordered
transactivation domain (TAD). We will determine the structure of inactive FoxM1, in which the TAD is
bound and sequestered by a negative regulatory domain (NRD). We will also test hypotheses for how
Cyclin-dependent and Polo-like kinases phosphorylate FoxM1, releasing the TAD from the NRD and
enhancing a helical structure that binds the transcription coactivator protein CBP. These studies will
provide fundamental new insights into cell cycle control through multisite phosphorylation and inform
future strategies for developing therapeutics that inhibit FoxM1 and its role in cell division.

## Key facts

- **NIH application ID:** 9878889
- **Project number:** 5R01GM127707-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Seth Michael Rubin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $272,559
- **Award type:** 5
- **Project period:** 2019-02-21 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878889

## Citation

> US National Institutes of Health, RePORTER application 9878889, Structural mechanisms of FoxM1 regulation (5R01GM127707-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9878889. Licensed CC0.

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