# Functions of thioredoxin reductases and their targets

> **NIH NIH R37** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $410,403

## Abstract

Redox biology is a rapidly expanding area of research. Recent studies have shown that the major cellular
processes are regulated by redox, yet specific mechanisnns are poorly understood. With the exception of
several exannples, the molecular targets of redox control, specificity of redox regulation, and the sets of
proteins that maintain cellular redox homeostasis are not known. Thiol-based redox regulation has emerged
as a prevalent mechanism to regulate cellular processes. Its major components, thioredoxin (Trx) and
thioredoxin reductase (TR), are present in nearly all organisms. TRs control the redox state of Trxs, which in
turn regulate cellular processes by controlling the redox state of cysteine (Cys) residues in proteins.
Mammals have three TRs, and all three contain catalytic selenocysteine (Sec) residues; therefore, the
mammalian Trx system is dependent on dietary selenium. Besides TRs and Trxs, numerous Trx-like
proteins and other thiol oxidoreductases (i.e., proteins that use catalytic redox Cys) exist, but their functions
are mostly unknown. It is also unknown which proteins are targeted by these enzymes. We would like to
characterize TRs, Trxs, thiol oxidoreductases and protein targets regulated by these proteins to define the
major pathways of thiol-based redox regulation in mammals. Specifically, we will carry out the following
studies: (1) Characterize organismal sets of thiol oxidoreductases and their protein targets using
bioinformatics, proteomics, and biochemical methods; (2) Analyze general features of thiol-based redox
regulation; (3) Characterize interplay between cysteine and selenocysteine in the active sites of
oxidoreductases; and (4) Examine interrelationship between hydrogen peroxide metabolism and thiol-based
redox control.
RELEVANCE (See instructions):
Thioredoxin reductase and thioredoxin are the main redox regulators of cysteines in proteins, whereby
controlling cellular processes. This system has been implicated in cell signaling, apoptosis, cancer
development, and many other physiological processes. We propose to characterize functions of thioredoxin
reductases, thiol oxidoreductases and their targets to define mechanisms of thiol-based redox regulation.

## Key facts

- **NIH application ID:** 9831642
- **Project number:** 5R37GM065204-19
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Vadim N. Gladyshev
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $410,403
- **Award type:** 5
- **Project period:** 2002-05-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9831642

## Citation

> US National Institutes of Health, RePORTER application 9831642, Functions of thioredoxin reductases and their targets (5R37GM065204-19). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9831642. Licensed CC0.

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