scholarly journals Selective auxin agonists induce specific AUX/IAA protein degradation to modulate plant development

2019 ◽  
Vol 116 (13) ◽  
pp. 6463-6472 ◽  
Author(s):  
Thomas Vain ◽  
Sara Raggi ◽  
Noel Ferro ◽  
Deepak Kumar Barange ◽  
Martin Kieffer ◽  
...  
Keyword(s):  
Small Molecules ◽  
Chromatin Remodeling ◽  
Plant Development ◽  
Chemical Biology ◽  
Auxin Signaling ◽  
Transcriptional Repressors ◽  
Transport Inhibitor ◽  
Specific Subset ◽  
Protein Ligases ◽  
Indole 3 Acetic Acid

Auxin phytohormones control most aspects of plant development through a complex and interconnected signaling network. In the presence of auxin, AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) transcriptional repressors are targeted for degradation by the SKP1-CULLIN1-F-BOX (SCF) ubiquitin-protein ligases containing TRANSPORT INHIBITOR RESISTANT 1/AUXIN SIGNALING F-BOX (TIR1/AFB). CULLIN1-neddylation is required for SCFTIR1/AFBfunctionality, as exemplified by mutants deficient in the NEDD8-activating enzyme subunit AUXIN-RESISTANT 1 (AXR1). Here, we report a chemical biology screen that identifies small molecules requiring AXR1 to modulate plant development. We selected four molecules of interest, RubNeddin 1 to 4 (RN1 to -4), among which RN3 and RN4 trigger selective auxin responses at transcriptional, biochemical, and morphological levels. This selective activity is explained by their ability to consistently promote the interaction between TIR1 and a specific subset of AUX/IAA proteins, stimulating the degradation of particular AUX/IAA combinations. Finally, we performed a genetic screen using RN4, the RN with the greatest potential for dissecting auxin perception, which revealed that the chromatin remodeling ATPase BRAHMA is implicated in auxin-mediated apical hook development. These results demonstrate the power of selective auxin agonists to dissect auxin perception for plant developmental functions, as well as offering opportunities to discover new molecular players involved in auxin responses.

scholarly journals Selective auxin agonists induce specific AUX/IAA protein degradation to modulate plant development

2018 ◽  
Author(s):  
Thomas Vain ◽  
Sara Raggi ◽  
Noel Ferro ◽  
Deepak Kumar Barange ◽  
Martin Kieffer ◽  
...  
Keyword(s):  
Small Molecules ◽  
Chromatin Remodeling ◽  
Plant Development ◽  
Chemical Biology ◽  
Auxin Signaling ◽  
Transcriptional Repressors ◽  
Transport Inhibitor ◽  
Specific Subset ◽  
Protein Ligases ◽  
Indole 3 Acetic Acid

AbstractAuxin phytohormones control most aspects of plant development through a complex and interconnected signaling network. In the presence of auxin, AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) transcriptional repressors are targeted for degradation by the SKP1-CULLIN1-F-BOX (SCF) ubiquitin-protein ligases containing TRANSPORT INHIBITOR RESISTANT 1/AUXIN SIGNALING F-BOX (TIR1/AFB). CULLIN1-neddylation is required for SCFTIR1/AFB functionality as exemplified by mutants deficient in the NEDD8-activating enzyme subunit AUXIN-RESISTANT 1 (AXR1). Here, we report a chemical biology screen that identifies small molecules requiring AXR1 to modulate plant development. We selected four molecules of interest, RubNeddin1 to 4 (RN1 to 4), among which RN3 and RN4 trigger selective auxin responses at transcriptional, biochemical and morphological levels. This selective activity is explained by their ability to promote the interaction between TIR1 and a specific subset of AUX/IAA proteins, stimulating the degradation of particular AUX/IAA combinations. Finally, via a genetic screen using RN4, we revealed that the chromatin remodeling ATPase BRAHMA is implicated in auxin-mediated apical hook development. These results demonstrate the power of selective auxin agonists to dissect auxin perception for plant developmental functions.

scholarly journals Local conjugation of auxin by the GH3 amido synthetases is required for normal development of roots and flowers in Arabidopsis

2021 ◽  
Author(s):  
Ruipan Guo ◽  
Yun Hu ◽  
Yuki Aoi ◽  
Hayao Hira ◽  
Chennan Ge ◽  
...  
Keyword(s):  
Amino Acids ◽  
Small Molecules ◽  
Plant Development ◽  
Gene Editing ◽  
Expression Patterns ◽  
Root Hairs ◽  
Genetic Redundancy ◽  
Group Ii ◽  
Indole 3 Acetic Acid

Gretchen Hagen 3 (GH3) amido synthetases conjugate amino acids to a carboxyl group of small molecules including hormones auxin, jasmonate, and salicylic acid. The Arabidopsis genome harbors 19 GH3 genes, whose exact roles in plant development have been difficult to define because of genetic redundancy among the GH3 genes. Here we use CRISPR/Cas9 gene editing technology to delete the Arabidopsis group II GH3 genes, which are able to conjugate indole-3-acetic acid (IAA) to amino acids. We show that plants lacking the eight group II GH3 genes (gh3 octuple mutants) accumulate free IAA and fail to produce IAA-Asp and IAA-Glu conjugates. Consequently, gh3 octuple mutants have extremely short roots, long and dense root hairs, and long hypocotyls and petioles. Our characterization of gh3 septuple mutants, which provide sensitized backgrounds, reveals that GH3.17 and GH3.9 play prominent roles in root elongation and seed production, respectively. We show that GH3 functions correlate with their expression patterns, suggesting that local deactivation of auxin also contributes to maintaining auxin homeostasis and is important for plant development. Moreover, this work provides a method for elucidating functions of individual members of a gene family, whose members have overlapping functions.

scholarly journals MicroRNAs Are Involved in Regulating Plant Development and Stress Response through Fine-Tuning of TIR1/AFB-Dependent Auxin Signaling

2022 ◽  
Vol 23 (1) ◽  
pp. 510
Author(s):  
Pan Luo ◽  
Dongwei Di ◽  
Lei Wu ◽  
Jiangwei Yang ◽  
Yufang Lu ◽  
...  
Keyword(s):  
Stress Response ◽  
Fine Tuning ◽  
Auxin Signaling ◽  
In Planta ◽  
Auxin Response ◽  
Signal Molecule ◽  
Master Regulators ◽  
Non Coding Rna ◽  
Complex Regulation ◽  
Indole 3 Acetic Acid

Auxin, primarily indole-3-acetic acid (IAA), is a versatile signal molecule that regulates many aspects of plant growth, development, and stress response. Recently, microRNAs (miRNAs), a type of short non-coding RNA, have emerged as master regulators of the auxin response pathways by affecting auxin homeostasis and perception in plants. The combination of these miRNAs and the autoregulation of the auxin signaling pathways, as well as the interaction with other hormones, creates a regulatory network that controls the level of auxin perception and signal transduction to maintain signaling homeostasis. In this review, we will detail the miRNAs involved in auxin signaling to illustrate its in planta complex regulation.

scholarly journals Small molecules with big roles in microRNA chemical biology and microRNA-targeted therapeutics

RNA Biology ◽  
2019 ◽  
Vol 16 (6) ◽  
pp. 707-718 ◽  
Author(s):  
Rengen Fan ◽  
Chaocheng Xiao ◽  
Xinqiang Wan ◽  
Wenzhang Cha ◽  
Yufeng Miao ◽  
...  
Keyword(s):  
Small Molecules ◽  
Chemical Biology ◽  
Targeted Therapeutics

The Role of MiRNAs in Auxin Signaling and Regulation During Plant Development

2017 ◽  
pp. 23-48 ◽  
Author(s):  
Clelia De-la-Peña ◽  
Geovanny I. Nic-Can ◽  
Johny Avilez-Montalvo ◽  
José E. Cetz-Chel ◽  
Víctor M. Loyola-Vargas
Keyword(s):  
Plant Development ◽  
Auxin Signaling

Target engagement approaches for pharmacological evaluation in animal models

2019 ◽  
Vol 55 (63) ◽  
pp. 9241-9250 ◽  
Author(s):  
James E. Kath ◽  
Aleksandra Baranczak
Keyword(s):  
Animal Models ◽  
Small Molecules ◽  
Chemical Biology ◽  
Target Engagement ◽  
Pharmacological Evaluation

We highlight recent applications of chemical biology approaches to measure target engagement of small molecules in animal models to support the nomination of clinical candidates.

scholarly journals From Phenotypic Hit to Chemical Probe: Chemical Biology Approaches to Elucidate Small Molecule Action in Complex Biological Systems

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5702
Author(s):  
Quentin T. L. Pasquer ◽  
Ioannis A. Tsakoumagkos ◽  
Sascha Hoogendoorn
Keyword(s):  
Small Molecules ◽  
Chemical Biology ◽  
Target Identification ◽  
Biologically Active ◽  
Phenotypic Screening ◽  
Biological Processes ◽  
Chemical Probes ◽  
Target Deconvolution ◽  
Cellular Target ◽  
Screening Approaches

Biologically active small molecules have a central role in drug development, and as chemical probes and tool compounds to perturb and elucidate biological processes. Small molecules can be rationally designed for a given target, or a library of molecules can be screened against a target or phenotype of interest. Especially in the case of phenotypic screening approaches, a major challenge is to translate the compound-induced phenotype into a well-defined cellular target and mode of action of the hit compound. There is no “one size fits all” approach, and recent years have seen an increase in available target deconvolution strategies, rooted in organic chemistry, proteomics, and genetics. This review provides an overview of advances in target identification and mechanism of action studies, describes the strengths and weaknesses of the different approaches, and illustrates the need for chemical biologists to integrate and expand the existing tools to increase the probability of evolving screen hits to robust chemical probes.

scholarly journals Chromatin Remodeling ATPases and Plant Development

2007 ◽  
Vol 19 (2) ◽  
pp. 394-394
Author(s):  
Nancy A. Eckardt
Keyword(s):  
Chromatin Remodeling ◽  
Plant Development
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