# Deubiquitinases in Cell Cycle Control

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $65,592

## Abstract

Project Summary Abstract
The focus of our current NIGMS funded R01 proposal (R01GM134231) is to study the role of deubiquitinating
enzymes in proliferation, cell cycle control and genome maintenance. The ubiquitin proteasome system is the
major regulator of protein degradation in all eukaryotes. Ubiquitination is implicated in virtually all aspects of
cell physiology and human disease. The post-translational conjugation of ubiquitin onto specific substrates
requires the concerted action of three enzymes, termed E1, E2 and E3. However, substrate ubiquitination and
degradation is determined not only by the addition of ubiquitin onto substrates, but also by the action of
catalytic proteases termed deubiquitinases (DUBs), which remove ubiquitin from substrates proteins, thereby
antagonizing degradation. The major goals of the parent R01 are to determine substrates and mechanisms of
deubiquitination during cell division, mechanisms of DUB action in the cell cycle, and the identity of additional
DUBs involved in cell cycle. The unifying theme of this research is the study of protein dynamics in cell cycle
progression. Determining the abundance of proteins in specific phases of the cell cycle is therefore vital to
determining the mechanisms underlying proteome remodeling and connecting enzymes with cognate
substrates. This analysis has significant technical challenges. First, many enzymes that control cell cycle
progression are themselves dynamically regulated, and their manipulation (e.g., knockdown or knockout) can
perturb cell cycle progression. Since the abundance of many cell cycle proteins, and particularly cell cycle
regulated ubiquitin substrates, is regulated as cells proliferate, their abundance can be altered by alterations to
the cell cycle. Thus, the ability to examine the abundance of specific proteins in specific cell cycle phases,
without the need for synchronization, is a tremendous advantage. We address these challenges through single
cell imaging. This current proposal requests support for the purchase of a Revolve R4 Echo Imaging System.
This instrument would allow our lab to perform imaging analysis in-house and would significantly improve the
capabilities of our current day-to-day tissue culture microscope, which lacks the ability of capture images,
precluding on-the-fly, quantitative analysis of transfection efficiencies or cell morphology. This purchase would
expand our current capabilities, facilitate orthogonal analysis methods that are easy to use and accessible, and
provide everyday access to improved cell culture processes.

## Key facts

- **NIH application ID:** 10582033
- **Project number:** 3R01GM134231-03S2
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Michael James Emanuele
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $65,592
- **Award type:** 3
- **Project period:** 2020-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10582033

## Citation

> US National Institutes of Health, RePORTER application 10582033, Deubiquitinases in Cell Cycle Control (3R01GM134231-03S2). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10582033. Licensed CC0.

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