# Control of protein degradation and transcriptional dynamics in the auxin response

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $304,673

## Abstract

The rate of protein turnover can act as a pacemaker to coordinate responses within and between cells, and is
frequently dysregulated in human disease. Yet we know remarkably little about what controls substrate
degradation kinetics or how these kinetics translate into downstream responses. One possible reason is the
lack of available models for high- resolution structure-function analysis of degradation and transcriptional
activation. The SCF class of E3 ubiquitin ligases is highly conserved among animals, plants and fungi. We
propose to use an SCF involved in auxin response, at the heart of nearly every aspect of plant biology, as a
model to investigate general principles underlying E3 function and connect that function to transcriptional
activation and morphogenesis. The small-molecule triggered degradation in the auxin pathway offers a unique
advantage for these studies, and has facilitated our engineering of auxin-induced degradation and
transcriptional activation in yeast. Work with this system has led to our central hypothesis: the auxin system
functions as a universal developmental timer in plants, and similar logic circuits likely act in most eukaryotes.
To test this hypothesis, we propose to: (1) Define the determinants and relevance of variation in degradation
rates. We have already identified several domains of interest in E3 and substrate components, and are using
synthetic and computational tools to connect individual residues to degradation dynamics. (2) Quantify the
impact of degradation rate on transcriptional repression. We have extended our synthetic assays to include
auxin-induced transcription. We can now quantitatively track the molecular events between substrate turnover
and downstream responses over time. This technology enables our study of previously intractable problems
like how the removal of co-repressors is integrated with transcriptional activation. (3) Couple cellular
degradation timers to developmental transitions. We have shown in transgenic plants that substrate
degradation rate sets the pace of lateral organ development. We will use multiple, complementary approaches
to analyze the transcriptome of these plants to elucidate how the timing of substrate turnover regulates
developmental progression in a cell-type-dependent manner. Together, the proposed work will provide a
mechanistic framework for E3 function in the auxin response and potentially provide insights into fundamental
properties of E3:substrate interactions and downstream events. These insights can inform our understanding
of E3s associated with human disease, as well as guiding future design of synthetic circuits using auxin
components for therapeutic applications.

## Key facts

- **NIH application ID:** 9896837
- **Project number:** 5R01GM107084-06
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** JENNIFER L NEMHAUSER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $304,673
- **Award type:** 5
- **Project period:** 2014-05-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896837

## Citation

> US National Institutes of Health, RePORTER application 9896837, Control of protein degradation and transcriptional dynamics in the auxin response (5R01GM107084-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9896837. Licensed CC0.

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