# Protein Arginylation as a Key Regulator of Cell Migration

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2020 · $666,403

## Abstract

Project Summary
The proposed work will address novel mechanisms of regulation of cell migration, building on two fundamental
paradigms that have been established through my independent work since 2004. First, I demonstrated the
essential biological role of protein arginylation and demonstrated that this posttranslational modification
regulates multiple proteins in vivo and critically affects cell migration. Second, I discovered that during cell
migration the coding sequence, rather than the amino acid sequence, drives functional distinction between
homologous protein isoforms by regulating their rates of translation, posttranslational modifications, and
function. This work, published in a number of high impact journals (including 18 peer reviewed publications in
the last 5 years) have established my lab as a leader in the field and the group uniquely suited to perform the
proposed studies.
We will combine these two innovative concepts into an integrated study that will uncover novel mechanisms of
the regulation of cell migration by mRNA coding sequence and arginylation. We hypothesize that: (1) mRNA-
mediated regulation of N-terminal arginylation of beta actin uniquely regulates actin function during cell
migration by facilitating actin polymerization at the cell leading edge; (2) ATE1's activity and targeting to
specific protein substrates and sites is regulated locally at the leading edge and/or globally throughout the cell
at the onset of cell migration and during changes in the migratory and metabolic state of the cell; and (3)
coding sequence coupled to arginylation constitute a novel fundamental mechanism that regulates
homologous protein isoforms involved in cell migration. Longer-term, our work will extend our cell migration-
related studies into a global concept for future studies that will determine the role of coding sequence and
arginylation in global protein regulation.

## Key facts

- **NIH application ID:** 9994752
- **Project number:** 5R35GM122505-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Anna S Kashina
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $666,403
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994752

## Citation

> US National Institutes of Health, RePORTER application 9994752, Protein Arginylation as a Key Regulator of Cell Migration (5R35GM122505-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9994752. Licensed CC0.

---

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