# Genetic requirements for executing SUMO stress signals and achieving stress tolerance

> **NIH NIH R15** · COLLEGE OF WILLIAM AND MARY · 2022 · $436,412

## Abstract

Project Summary/Abstract:
Temperature, radiation, oxidizing reagents, as well as shear and osmotic stress are
environmental, extrinsic stressors that cause tissue and cellular damage. There is good
evidence that organisms as diverse as yeast and humans utilize SUMO modification as part of
their cellular stress response. SUMO is a small proteinaceous modifier that can be covalently
linked to specific target proteins, affecting their activity, localization, interactions, and half-life.
This project focuses on the SUMO Stress Response (SSR), the rapid increase of protein
sumoylation after cells experience acute proteotoxic stress. The SSR is believed to play a cyto-
protective role for normal cells, but it may also enhances the robustness of cancerous cells and
some eukaryotic pathogens. Stress-induced sumoylation has profound effects on transcriptional
reprogramming and protein complex integrity in the nucleus. However, there is little or no
knowledge how the SSR affects cytoplasmic processes including cytoskeletal rearrangements,
mitochondrial inheritance, vesicle sorting, and translation. Here we use the genetically tractable
yeast Sacharomyces cerevisiae to address our hypothesis that cross-talk between protein
sumoylation and ubiquitination in the cytoplasm plays a central role in cytoprotective effects
initiated by dynamic stress-induced sumoylation. The specific aims of this project are 1) to use
cell biological and genetic approaches, and an innovative yeast SUMO Stress Reporter strain,
to dissect the choreography of the SSR. Specifically, to investigate evidence of stress-induced
cooperativity of the SUMO E3 ligase Siz1 and the NEDD4/Rsp5 E3 ubiquitin ligase in the
cytoplasm that may exert stress-induced control over cytoskeleton organization, mitochondrial
inheritance, vesicle sorting, and translation. 2) To analyze a group of potential cytoplasmic SSR
effector proteins we identified and to examine the functional consequences of genetic defects
that result in their dysfunction. 3) To use innovative methods to identify variant SUMO pathway
components that promote stress tolerance with the goal to ultimately test clinically-relevant
alleles of SUMO pathway genes that may affect stress tolerance and the likelihood of cancer
development. Our project is well-aligned with AREA program goals and will expose
undergraduate students to meritorious research that is biomedically relevant.

## Key facts

- **NIH application ID:** 10514836
- **Project number:** 1R15GM147883-01
- **Recipient organization:** COLLEGE OF WILLIAM AND MARY
- **Principal Investigator:** Oliver none Kerscher
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $436,412
- **Award type:** 1
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10514836

## Citation

> US National Institutes of Health, RePORTER application 10514836, Genetic requirements for executing SUMO stress signals and achieving stress tolerance (1R15GM147883-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10514836. Licensed CC0.

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