The plant hormone auxin is involved in virtually all aspects of plant growth and development. Remarkably, auxin exerts its affects over a broad concentration range. At the cellular level, auxin acts to regulate cell expansion, cell division, ad cell fate. One of the most interesting and challenging questions in plant biology is how this simple molecule elicits such a complex set of responses. We have focused on auxin regulation of transcription. Over the years, we have shown that auxin acts by stimulating the degradation of a family of transcriptional repressors called the Aux/IAA proteins, through the action of the ubiquitin protein ligase SCFTIR1/AFB. During the last grant period we demonstrated that auxin is perceived by a co-receptor consisting of TIR1 or an AFB protein plus an Aux/IAA protein. Importantly, different co-receptor pairs differ in their affinity for auxin. The existence of high nd low affinity co-receptors dramatically enhances the dynamic range of the hormone and may contribute to the complexity of auxin responses. In addition, our recent work led to the discovery that the chaperone HSP90 and co-chaperone SGT1 are involved in TIR1 function, and that auxin response in the hypocotyl or seedling stem, is facilitated by a positive feedback loop that involves a family of proteins called the PREs. The long-term goals of this proposal are to determine the molecular basis of auxin signaling.
Our specific aims are to 1) test the biological significance of the auxin co-receptor model, 2) to investigate the role of HSP90 and SGT1 in SCFTIR1 function, 3) to characterize the PRE positive feedback loop in auxin-regulated hypocotyl elongation. These studies address a number of key issues in cellular regulation and will have important implications for human health. The ubiquitin pathway and the SCFs in particular are involved in diverse disease processes including numerous cancers. Because SCFTIR1 is one of the best- characterized E3 complexes in any organism, this work provides a unique opportunity to advance our understanding of this critical aspect of human disease.

Public Health Relevance

Protein homeostasis is a central aspect of cellular regulation. Defects in pathways that mediate protein stability and degradation including the chaperones and the ubiquitin proteasome pathway contribute to many disease processes including cancers. This study will advance our understanding of the protein homeostasis in cell function.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM043644-26A1
Application #
8642857
Study Section
Cellular Signaling and Regulatory Systems Study Section (CSRS)
Program Officer
Maas, Stefan
Project Start
1989-08-01
Project End
2018-02-28
Budget Start
2014-05-01
Budget End
2015-02-28
Support Year
26
Fiscal Year
2014
Total Cost
$286,532
Indirect Cost
$96,532
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Lavy, Meirav; Estelle, Mark (2016) Mechanisms of auxin signaling. Development 143:3226-9
Prigge, Michael J; Greenham, Kathleen; Zhang, Yi et al. (2016) The Arabidopsis Auxin Receptor F-Box Proteins AFB4 and AFB5 Are Required for Response to the Synthetic Auxin Picloram. G3 (Bethesda) 6:1383-90
Lavy, Meirav; Prigge, Michael J; Tao, Sibo et al. (2016) Constitutive auxin response in Physcomitrella reveals complex interactions between Aux/IAA and ARF proteins. Elife 5:
Tal, Iris; Zhang, Yi; Jørgensen, Morten Egevang et al. (2016) The Arabidopsis NPF3 protein is a GA transporter. Nat Commun 7:11486
Wang, Renhou; Zhang, Yi; Kieffer, Martin et al. (2016) HSP90 regulates temperature-dependent seedling growth in Arabidopsis by stabilizing the auxin co-receptor F-box protein TIR1. Nat Commun 7:10269
Estelle, Mark (2016) Moss tasiRNAs Make the Auxin Network Robust. Dev Cell 36:241-2
Yu, Hong; Zhang, Yi; Moss, Britney L et al. (2015) Untethering the TIR1 auxin receptor from the SCF complex increases its stability and inhibits auxin response. Nat Plants 1:
Gao, Yangbin; Zhang, Yi; Zhang, Da et al. (2015) Auxin binding protein 1 (ABP1) is not required for either auxin signaling or Arabidopsis development. Proc Natl Acad Sci U S A 112:2275-80
Gilkerson, Jonathan; Kelley, Dior R; Tam, Raymond et al. (2015) Lysine Residues Are Not Required for Proteasome-Mediated Proteolysis of the Auxin/Indole Acidic Acid Protein IAA1. Plant Physiol 168:708-20

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