Hormone-mediated modulation of gene activation or repression through transcription factors is central to all organisms. Auxin Response Factor (ARF) transcription factors are critical modulators of plant growth and provide an ideal model for exploring hormone control of gene activation and repression. We have recently identified protein multimerization and proteasomal degradation as two previously unknown mechanisms that regulate ARF activity. The long-term goal of this research project is to determine the importance of these ARF regulatory mechanisms in Arabidopsis thaliana transcriptional control. Elucidating the molecular mechanism of ARF regulation likely will uncover control processes common to other transcription factors. A repression-derepression paradigm regulates ARF activity. Under low concentrations of the hormone auxin, ARF transcriptional activity is repressed by Aux/IAA repressor proteins. When auxin concentrations increase, a co-receptor complex, comprised of an F-box protein (TIR1) and an Aux/IAA repressor protein, directly binds auxin. The F-box protein participates in a Skp1-Cullin-F-box (SCF) E3 ubiquitin ligase, which targets the Aux/IAA protein for degradation. This degradation event relieves ARF repression, thereby allowing auxin-regulated gene transcription. Although this molecular model of repression and derepression for auxin activity appears relatively simple, our recent preliminary data suggest several exciting new control components and posttranslational modifiers influence ARF transcriptional activity and protein accumulation. This project aims to elucidate auxin signaling molecular mechanisms by identifying regulators of ARF protein activity and accumulation. To achieve this goal, we will use a combination of biochemical, biophysical, cell biology, synthetic biology, molecular and genetic techniques to gain insight into factors that influence ARF activity.
The first aim i s to understand the role of protein multimerization in the regulation of ARF transcriptional activity. Studies in both a synthetic yeast auxin response system and in planta will be used to test aspects of this aim, which includes functional assays and 3C analysis.
The second aim i s understand the role of multimerization in the regulation of ARF localization. We will determine whether ARF posttranslational modification affects ARF cellular localization.
Our third aim i s to establish rols for ARF proteasome-dependent degradation in regulating auxin response and plant development. We will use a variety of genetic, biochemical, and cell biology techniques to understand the biological and developmental roles for regulated ARF stability. The proposed research is innovative because our approaches focus strongly on the molecular understanding of ARF regulation, guided by our recent structural data on ARF7 and it has the potential to dramatically alter the auxin signaling model. The proposed research is significant because it is expected to advance and expand understanding of transcription factor regulation, using ARF factors as a model.

Public Health Relevance

Part of the NIH mission is to seek fundamental knowledge about the nature and behavior of living systems. The proposed research is relevant to the NIH mission because it seeks to understand hormone-mediated modulation of gene activation or repression through transcription factors. Because this process is central to all systems, identifying mechanisms that regulate transcriptional activity in one organism may be broadly informative to all organisms, including humans.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Development - 1 Study Section (DEV1)
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Melillo, Amanda A
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Washington University
Schools of Arts and Sciences
Saint Louis
United States
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Frick, E M; Strader, L C (2018) They Can Handle the Stress: MPK17 and PMD1 act in a salt-specific pathway. Plant Signal Behav 13:e1428518
Frick, Elizabeth M; Strader, Lucia C (2018) Kinase MPK17 and the Peroxisome Division Factor PMD1 Influence Salt-induced Peroxisome Proliferation. Plant Physiol 176:340-351
Frick, Elizabeth M; Strader, Lucia C (2018) Roles for IBA-derived auxin in plant development. J Exp Bot 69:169-177
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