# Development of Activity-Based Chemical Reporters to Differentiate Proteasome Isoforms in Cells

> **NIH NIH R21** · PURDUE UNIVERSITY · 2020 · $193,750

## Abstract

Project Summary
 The proteasome plays a significant role in the proper functioning of eukaryotic cells. It is responsible for up
to 90% of the cell's protein degradation needs, controls cell pathways with the proper balance of critical protein
levels, and produces antigenic peptides to allow the immune system to recognize diseased cells. To meet these
diverse needs of the organism, different forms of the proteasome exist with corresponding specialties. There are
limited tools available to analyze the different types of proteasome isoform activities in the cells.
 Proteasome mediated protein hydrolysis can occur through at least three different paths. The tools currently
available cannot effectively differentiate between the activity of these proteasome isoforms and are easily
hydrolyzed by other proteases in the cell. The goal of this project is to design proteasome isoform-selective
activity probes. We will extensively utilize the data accumulated to produce selective inhibitors to design our
activity probes. Upon completion of this project, we will have new proteasome activity probes that can
differentiate the activity of ubiquitin-dependent and -independent degradation. We will also have a probe that
can detect protein hydrolysis mediated by the immunoproteasome only. The design of our probes will also include
significant secondary structure and peptidomimetic subunits to prevent non-specific hydrolysis by proteases in
cells.
 Distinguishing the activity of the types of proteasomes within a cell would clarify which protein degradation
pathway could be targeted as a new therapy. We anticipate they can be used to monitor the amount of ubiquitin-
dependent and -independent degradation in protein accumulation diseases and in hematological cancers. The
immunoproteasome has recently been implicated in a variety of autoimmune diseases and type I diabetes. Our
probes will provide a way to determine how much immunoproteasome activity affects these diseases. We believe
these new probes will fill an empty niche in the proteasome field for when one wants to study the activity of an
individual proteasome isoform.

## Key facts

- **NIH application ID:** 10001555
- **Project number:** 5R21GM131206-02
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Darci J Trader
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,750
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001555

## Citation

> US National Institutes of Health, RePORTER application 10001555, Development of Activity-Based Chemical Reporters to Differentiate Proteasome Isoforms in Cells (5R21GM131206-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001555. Licensed CC0.

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