# Expanding Roles of E2 and E3 Enzymes in Ubiquitin Transfer

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $543,642

## Abstract

The regulatory process known as protein ubiquitination modifies cellular proteins with 
far-­reaching impacts on human health and disease. It is involved in every known 
biological process and is implicated in a growing range of diseases that includes 
cancers, neurodegenerative diseases, muscle wasting, etc. Studies conducted 
worldwide over the past twenty years have defined the mechanisms by which protein 
ubiquitination is carried out, with one obvious exception. Almost little is known about how 
substrates (i.e., the cellular proteins that are modified by this system) are recognized 
and how they fit into the ultimate mechanism. In the coming grant period, we propose to 
rectify this situation for two important ubiquitin E3 ligases, BRCA1/BARD1 and HHARI. 
Our goals are made possible by several important advances, including definition of bona 
fide substrates for each of these E3s and the ability to chemically synthesize 
biochemically homogeneous version of the products. We will also investigate two 
uncharacterized human E2 Ubiquitin-­conjugating enzymes that each have 
unusual/unique activities in that they attach Ub to protein groups other than lysines, 
thereby expanding the universe of possible attachment sites. We will use a combination 
of biochemical, structural, and cellular approaches to address questions of fundamental 
importance and general relevance.

## Key facts

- **NIH application ID:** 9995481
- **Project number:** 5R01GM088055-21
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Rachel E Klevit
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $543,642
- **Award type:** 5
- **Project period:** 1998-12-21 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995481

## Citation

> US National Institutes of Health, RePORTER application 9995481, Expanding Roles of E2 and E3 Enzymes in Ubiquitin Transfer (5R01GM088055-21). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9995481. Licensed CC0.

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