The plant hormone auxin is involved in virtually all aspects of plant growth and development. Over the years we and others have demonstrated 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. Although this basic pathway is well established, we still know very little about how auxin regulates plant growth and development. Strikingly, auxin-regulated genes differ dramatically between cell types and organs, consistent with the diverse roles of the hormone. The basis for this specificity is unknown. Similarly, the activities of the Aux/IAA and ARF proteins are poorly characterized and the transcriptional networks (GRNs) that mediate various auxin-regulated growth processes have not been defined. Finally, we know little about how auxin signaling is integrated with other environmental and genetic signaling pathways. During the last grant period we demonstrated that the 6 members of the AFB family of F-box proteins act in an additive fashion but may also have specific functions. In addition, our recent ChIPseq experiments indicate that the AFB proteins are bound to chromatin adjacent to auxin-regulated genes and are recruited to these sites by auxin. We speculate that the close association of SCFAFB with chromatin permits rapid de- repression of auxin responsive genes. We also made significant advances in our understanding of the Aux/IAA proteins and the architecture of the auxin signaling network. Our work shows that the Aux/IAA genes function as regulatory nodes that integrate environmental signals with the auxin gene regulatory network. Most exciting, we have shown that the DREB2-dependent but ABA-independent abiotic stress response pathway acts through the Aux/IAAs to mediate drought tolerance. Further we demonstrate that this pathway regulates the levels of secondary products called glucosinolates and that these compounds promote stomatal closure and drought tolerance. These studies indicate that glucosinolates have previously unknown signaling properties. The long-term goals of this proposal are to determine the molecular basis of auxin signaling and to characterize the auxin-based regulatory networks that control plant growth and development.
Our specific aims are to; 1) Investigate the role of the IAA5,6,19 protein in DREB2-mediated drought tolerance, 2) Determine the mechanism of Aux/IAA-based transcriptional repression, 3) Explore the specificity of the AFB and Aux/IAA proteins, and 4) Investigate recruitment of AFBs to chromatin. 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 SCFTIR/AFB1 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 and hormone signaling are central aspects of cellular regulation. Defects in pathways that mediate protein stability and hormone signaling contribute to many disease processes including cancers. This study will advance our understanding of the protein homeostasis and hormone signaling in cell function.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM043644-30
Application #
9661646
Study Section
Cellular Signaling and Regulatory Systems Study Section (CSRS)
Program Officer
Melillo, Amanda A
Project Start
1989-08-01
Project End
2023-01-31
Budget Start
2019-02-01
Budget End
2020-01-31
Support Year
30
Fiscal Year
2019
Total Cost
Indirect Cost
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
Tao, Sibo; Estelle, Mark (2018) Mutational studies of the Aux/IAA proteins in Physcomitrella reveal novel insights into their function. New Phytol 218:1534-1542
Bagchi, Rammyani; Melnyk, Charles W; Christ, Gideon et al. (2018) The Arabidopsis ALF4 protein is a regulator of SCF E3 ligases. EMBO J 37:255-268
Iglesias, María José; Terrile, María Cecilia; Correa-Aragunde, Natalia et al. (2018) Regulation of SCFTIR1/AFBs E3 ligase assembly by S-nitrosylation of Arabidopsis SKP1-like1 impacts on auxin signaling. Redox Biol 18:200-210
Ligerot, Yasmine; de Saint Germain, Alexandre; Waldie, Tanya et al. (2017) The pea branching RMS2 gene encodes the PsAFB4/5 auxin receptor and is involved in an auxin-strigolactone regulation loop. PLoS Genet 13:e1007089
Shani, Eilon; Salehin, Mohammad; Zhang, Yuqin et al. (2017) Plant Stress Tolerance Requires Auxin-Sensitive Aux/IAA Transcriptional Repressors. Curr Biol 27:437-444
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:
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

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