# Exploiting bacterial effector proteins to study human ubiquitin signaling

> **NIH NIH R35** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $385,000

## Abstract

Project Summary
 Post-translational signaling through ubiquitination is essential to all eukaryotic life, and dysregulation of this
process can lead to severe forms of disease. The far-reaching importance of ubiquitin signaling across many
cellular processes stems from its ability to form a diverse set of polymeric chains that signal for distinct
outcomes. The complexity of ubiquitin signaling vastly outweighs our understanding of its regulation and
cellular outcomes. While the signaling roles for some ubiquitin chain types are known (e.g. protein degradation
or cell cycle regulation), the functions of many so-called `atypical' chains have remained a mystery despite
decades of research. As an alternative approach to studying fundamental human biology, we study the
interactions between invading pathogenic bacteria and the host ubiquitin signaling network. In addition to a
range of other ubiquitin-targeted activities, to support infection bacteria have evolved secreted effector proteins
to assemble and remove host ubiquitin signals, in some cases with exquisite specificity toward discrete
ubiquitin chain types. We propose that ubiquitin-targeted bacterial effectors represent a rich opportunity to
study human ubiquitin signaling from an `outside-in' perspective. To explore this opportunity, we have
developed a multipronged approach that has identified novel ubiquitin-targeted activities among important
bacterial pathogens. Using structural and biochemical approaches we will explain the mechanisms and
specificities of these bacterial enzymes, at which point they will be used as case studies and tools to extend
our work toward deciphering the regulatory and signaling complexities of the human ubiquitin system. Our
innovative approach to studying ubiquitin biology plays to our strengths in the biochemical mechanisms of its
regulation, and leverages the strong evolutionary pressure placed on bacteria to usurp specific aspects of host
ubiquitin signaling. Over the next five years we will demonstrate the breadth of bacterial ubiquitin-targeted
activities and their utility for dissecting the intricacies of ubiquitin signaling, which feeds into our larger vision of
understanding the motivations and ramifications of bacterial interference in host signaling processes.

## Key facts

- **NIH application ID:** 10436347
- **Project number:** 5R35GM142486-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jonathan N Pruneda
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436347

## Citation

> US National Institutes of Health, RePORTER application 10436347, Exploiting bacterial effector proteins to study human ubiquitin signaling (5R35GM142486-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10436347. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*