# Regulation by post-translation modifications in response to stress

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $25,772

## Abstract

Project Summary/Abstract
Ubiquitin ligases (E3s) represent a diverse and conserved group of enzymes, with over
600 members. These ligases collectively attach the small protein ubiquitin to more than
twenty five percent of the proteome, thereby regulating the stability or activity of each
target. Despite the importance of this set of enzymes, only a small percentage of
ubiquitin ligases have well-characterized biological functions. We have conducted a
CRISPR screen examining the sensitivity of mutations of genes encoding human
ubiquitin ligases and deubiquitinating enzymes to a panel of inhibitors covering a broad
range of biological pathways. From this screen, we identified an F box protein, called
FBXO42, whose mutation renders cells sensitive to inhibitors of mitosis and causes the
accumulation of cells with mitotic defects. F box proteins are substrate adaptors for the
SCF cullin RING ligase. One of the greatest challenges in the study of ubiquitin ligases
is identifying their substrates. We developed several methods to accomplish this, using
(MS) spectrometry and fluorescent detection. Leah will identify mitotic substrates of
FBXO42 using "ligase trap" fusion proteins and through genetic screens. By identifying
FBXO42 substrates, we will be able to better understand its role in the cell cycle.

## Key facts

- **NIH application ID:** 10098111
- **Project number:** 3R35GM118104-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** David Paul Toczyski
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $25,772
- **Award type:** 3
- **Project period:** 2016-05-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10098111

## Citation

> US National Institutes of Health, RePORTER application 10098111, Regulation by post-translation modifications in response to stress (3R35GM118104-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10098111. Licensed CC0.

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