# Regulation of ARF tumor suppressor function by biological phase separation

> **NIH NIH F32** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $67,446

## Abstract

PROJECT SUMMARY
 The proposed study aims to determine how phase separation regulates the ARF protein, a tumor suppressor
that frequently experiences loss of function in human cancers. During oncogenic stress, ARF sequesters
essential proteins in the nucleolus in order to arrest the cell cycle or induce apoptosis. Specifically, ARF
sequesters HDM2 in the nucleolus, which activates p53-dependent cell cycle arrest or apoptosis. ARF also
sequesters NPM1 in the nucleolus, disrupting ribosome assembly, which also induces cell cycle arrest
independently of p53. However, the mechanism by which ARF sequesters its targets in the nucleolus is not
understood.
 Recent observations have demonstrated that nucleoli possess liquid-like properties, which manifest through
phase separation of their constituent proteins and RNAs. Recently, our lab along with the Brangwynne group,
showed that the liquid like features of the nucleolus depends in-part on the phase separation properties of NPM1.
I hypothesize that p14ARF disrupts the liquid-like properties of the granular component through
hydrophobic self-association and multivalent interactions of its multiple arginine-rich motifs with NPM1,
resulting in inhibition of ribosome biogenesis.
 This study will determine (1) how p14ARF’s physicochemical properties allow it to sequester its target
proteins within phase separated bodies, (2) the structure and dynamics of phase separated p14ARF-NPM1
complexes, and (3) the effect of p14ARF expression on NPM1 dynamics, ribosome biogenesis and growth
in live cells. Results from this study will provide novel insights into ARF’s nucleolar tumor suppressor function,
and in a broader context, how the fluid-features of nucleoli are altered during oncogenic stress events.

## Key facts

- **NIH application ID:** 10065965
- **Project number:** 1F32GM133078-01A1
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Eric B Gibbs
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 1
- **Project period:** 2020-07-09 → 2021-07-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065965

## Citation

> US National Institutes of Health, RePORTER application 10065965, Regulation of ARF tumor suppressor function by biological phase separation (1F32GM133078-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10065965. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*