# Chemistry and Biology of ADP-Ribosylation-Dependent Signaling

> **NIH NIH R35** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $394,433

## Abstract

Abstract
 Protein ADP-ribosylation is a complex and highly dynamic process regulated by distinct writer, reader and
eraser proteins. As a key post-translational modification, protein ADP-ribosylation is catalyzed by ADP-
ribosyltransferases (ARTs) by using nicotinamide adenine dinucleotide (NAD+) as a co-substrate and plays
important roles in regulating a significant number of physiological and pathophysiological processes. ADP-
ribosylated proteins can be recognized by reader proteins, triggering downstream signaling cascades or effector
functions in direct or indirect manners. The ADP-ribosylation-mediated signaling can be modulated by eraser
proteins that rapidly remove covalently attached ADP-ribose unit(s). In addition to their extensive involvements
in physiological events, the writers, readers, and erasers of protein ADP-ribosylation are broadly implicated in
numerous diseases. However, it remains elusive for the functions and roles of ADP-ribosylation in human health
and pathogenesis of many diseases. Despite technological advancement, little information is known regarding
the identity of the reader(s) and eraser(s) for individual ADP-ribosylated proteins, the preferred ADP-ribosylated
protein(s) for a specific reader or eraser protein, and the ADP-ribosylation-centered interaction networks. And
tools and technologies have yet to be developed for unambiguously mapping ADP-ribosylation-dependent
interactome. The goal of this MIRA project is to develop novel chemical tools to address these major challenges.
In next five years, we are aimed to generate novel bifunctional NAD+ molecules for unbiased and faithful
dissection of ADP-ribosylation-dependent interactome and define their roles in cell signaling. Successful
completion of this work will result in a set of novel and important chemical tools for addressing challenges in
research on ADP-ribosylation-dependent events and processes across multiple areas. These innovative tools
may lead to major breakthroughs in understanding of the cellular functions and regulatory roles of protein ADP-
ribosylation in physiology and pathophysiology and in the development of novel diagnostics and therapeutics
targeting ADP-ribosylation-associated activities and pathways for many human diseases.

## Key facts

- **NIH application ID:** 10026899
- **Project number:** 1R35GM137901-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Yong Zhang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $394,433
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10026899

## Citation

> US National Institutes of Health, RePORTER application 10026899, Chemistry and Biology of ADP-Ribosylation-Dependent Signaling (1R35GM137901-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10026899. Licensed CC0.

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