# Characterizing new redox roles for protein ubiquitination in human cells

> **NIH NIH R21** · DUKE UNIVERSITY · 2022 · $421,492

## Abstract

PROJECT SUMMARY
Human cells are constantly subjected to oxidative stress due to the exposure to solar UV radiation and to
pollutants in the water and in the atmosphere. To cope with the harms of oxidative stress that can lead to cellular
malfunction and death, cells must reprogram gene expression and adjust the dynamics of protein production and
degradation. Ubiquitin is a prominent protein modifier that controls the fate and the function of numerous proteins,
and reshapes the proteome during environmental stresses. In response to oxidative stress, thousands of proteins
accumulate ubiquitin modification and are involved in a variety of functions that support cellular survival. My lab
discovered a new ubiquitin-dependent pathway that regulates protein production in yeast; however little is known
about the importance and regulation of this pathway in human cells. In addition, to modify a large number of
proteins with ubiquitin, human cells rely on hundreds of ubiquitin enzymes that selectively recognize their
dedicated targets. However, the contribution of each ubiquitin enzyme to cellular resistance to stress is largely
unknown. The purpose of the proposed project is to identify and characterize the roles of ubiquitin as a master
regulator of the stress response. In Aim 1, we will investigate the molecular details of localized ubiquitin
accumulation under oxidative stress, including when, why, and how it occurs. In Aim 2, we will investigate
different aspects of cellular response to stress using genome editing methodologies targeting functional domains
of > 700 ubiquitin enzymes. As oxidative stress is the underlying cause of a variety of human conditions such as
aging, tumor progression, and degenerative disease, our research will provide a new understanding of ubiquitin
function in the promotion of cellular health. Defining the importance of these pathways and the physiological role
of ubiquitin enzymes will provide several avenues for drug development and it will allow us to learn the
fundamental principles of the enzymatic regulation of protein ubiquitination during cellular resistance to stress.

## Key facts

- **NIH application ID:** 10371928
- **Project number:** 1R21ES032964-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Gustavo M Silva
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $421,492
- **Award type:** 1
- **Project period:** 2022-09-05 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371928

## Citation

> US National Institutes of Health, RePORTER application 10371928, Characterizing new redox roles for protein ubiquitination in human cells (1R21ES032964-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10371928. Licensed CC0.

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