# Modulation of Runx2 activity by arginine methylation

> **NIH NIH R21** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $206,250

## Abstract

PROJECT SUMMARY / ABSTRACT
Protein arginine methylation is a rapidly growing field with increasingly recognized importance in cancer, but
almost nothing is known about this mechanism in bone. This proposal is based on novel discoveries on the
arginine methylation of Runx2. We have identified two protein arginine methyltransferases that methylate
Runx2 on four defined arginine residues. By mutating these residues to alanine that mimic the methylation-
deficient state, we have demonstrated the requirement for Runx2 arginine methylation in Runx2-mediated
cancer cell motility. Here, we will investigate Runx2 arginine methylation in the context of its canonical role in
osteoblast differentiation and bone formation. Aim 1 is to characterize the temporal arginine methylation of
Runx2 in osteogenic cell culture models. We will also compare the osteogenic potentials of WT Runx2 versus
unmethylatable mutant Runx2, and the consequences of manipulating methyltransferases that mediate Runx2
methylation. Aim 2 addresses the role of Runx2 arginine methylation in modulating the physical and functional
interaction with BMP-Smads pathway. Finally, Aim 3 is to define the arginine methylation of Runx2, and the
expression of methyltransferases that mediate Runx2 methylation during skull development in vivo, and to
compare the osteogenic potential of WT versus unmethylatable Runx2 in calvarial organ cultures. Overall, this
proposal addresses the hypothesis that arginine methylation is required for Runx2 activity during osteogenic
differentiation and essential for BMP-Smad signaling response. Additionally, we have incorporated in the study
design genomic and proteomic analyses to facilitate unbiased discoveries of Runx2 protein-protein
interactions, Runx2 genomic targets and Runx2-regulated genes that are impacted by its arginine methylation.
In the long run, we envision translation of knowledge acquired in this exploratory project to improve the
understanding of bone development, homeostasis and regeneration, and provide novel therapeutic
approaches to tackle skeletal disorders.

## Key facts

- **NIH application ID:** 9903272
- **Project number:** 5R21DE028617-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Jian Xu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $206,250
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903272

## Citation

> US National Institutes of Health, RePORTER application 9903272, Modulation of Runx2 activity by arginine methylation (5R21DE028617-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9903272. Licensed CC0.

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