Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.25.1 (proteasome)
28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Auxin rapidly induces auxin/indoleacetic acid (Aux/IAA) transcription. The proteins encoded are short-lived nucleus-localized transcriptional regulators that share four conserved domains. In a transient assay measuring protein accumulation, an Aux/IAA 13-amino acid domain II consensus sequence was sufficient to target firefly luciferase (LUC) for low protein accumulation equivalent to that observed previously for full-length PSIAA6. Single amino acid substitutions in these 13 amino acids, corresponding to known auxin response mutants, resulted in a sixfold to 20-fold increase in protein accumulation. Naturally occurring variant amino acids had no effect. Residues identified as essential by single alanine substitutions were not sufficient when all flanking amino acids were alanine, indicating the importance of flanking regions. Using direct protein degradation measurements in transgenic Arabidopsis seedlings, full-length IAA1, PSIAA6, and the N-terminal 73 PSIAA6 amino acids targeted LUC for rapid degradation with 8-min half-lives. The C-terminal 109 amino acids did not affect LUC half-life. Smaller regions containing domain II also targeted LUC for rapid degradation, but the rates were not equivalent to those of the full-length protein. A single domain II substitution in the context of full-length PSIAA6 increased half-life 30-fold. Proteasome inhibitors affected Aux/IAA::LUC fusion protein accumulation, demonstrating the involvement of the proteasome.
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PMID:Rapid degradation of auxin/indoleacetic acid proteins requires conserved amino acids of domain II and is proteasome dependent. 1170 83

Despite recent progress auxin signal transduction remains largely scetchy and enigmatic. A good body of evidence supports the notion that the ABP1 could be a functional receptor or part of a receptor, respectively, but this is not generally accepted. Evidence for other functional receptors is lacking, as is any clearcut evidence for a function of G proteins. Protons may serve as second messengers in guard cells but the existing evidence for a role of calcium remains to be clearified. Phospholipases C and D seem not to have a function in auxin signal transduction whereas the indications for a role of phospholipase A2 in auxin signal transduction accumulated recently. Mitogen-activated protein kinase (MAPK) is modulated by auxin and the protein kinase PINOID has a role in auxin transport modulation even though their functional linkage to other signalling molecules is ill-defined. It is hypothesized that signal transduction precedes activation of early genes such as IAA genes and that ubiquitination and the proteasome are a mechanism to integrate signal duration and signal strength in plants and act as major regulators of hormone sensitivity.
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PMID:Secondary messengers and phospholipase A2 in auxin signal transduction. 1203 60

Auxin signaling relies on ubiquitin ligase SCF(TIR1)-mediated 26S proteasome-dependent proteolysis of a large family of short-lived transcription regulators, auxin/indole acetic acid (Aux/IAA), resulting in the derepression of auxin-responsive genes. We have shown previously that a subset of Rac GTPases is activated by auxin, and they in turn stimulate auxin-responsive gene expression. We show here that increasing Rac signaling activity promotes Aux/IAA degradation, whereas downregulating that activity results in the reduction of auxin-accelerated Aux/IAA proteolysis. Observations reported here reveal a novel function for these Rac GTPases as regulators for ubiquitin/26S proteasome-mediated proteolysis and further consolidate their role in auxin signaling. Moreover, our study reveals a cellular process whereby auxin induces and Rac GTPases mediate the recruitment of nucleoplasmic Aux/IAAs into proteolytically active nuclear protein bodies, into which components of the SCF(TIR1), COP9 signalosome, and 26S proteasome are also recruited.
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PMID:RAC GTPases in tobacco and Arabidopsis mediate auxin-induced formation of proteolytically active nuclear protein bodies that contain AUX/IAA proteins. 1599 9

Auxin regulates many aspects of plant growth and development by altering the expression of diverse genes. Among these, the early auxin-responsive genes of Aux/IAA class have been extensively studied in dicots but little information is available on monocots. Earlier, we reported the isolation of OsiIAA1 cDNA, first monocot member of Aux/IAA gene family from rice. Extending this work further, we have isolated the OsiIAA1 gene from rice localized on chromosome 3. The transcriptional start site was mapped to 158 bp upstream to the translational start site. The increased accumulation of OsiIAA1 transcript in auxin-treated rice coleoptiles even in the presence of a protein synthesis inhibitor, cycloheximide, suggested that OsiIAA1 is a primary auxin response gene; the expression of OsiIAA1 gene was also upregulated in the presence of cycloheximide alone. The OsiIAA1 transcript levels were down-regulated in etiolated rice coleoptiles irradiated with far-red, red and blue light, suggesting the existence of a cross-talk between auxin and light signaling. The antibodies raised against His6-OsiIAA1 recombinant protein could detect the OsiIAA1 protein in the plant extract only in the presence of a proteasome inhibitor, MG132, indicating that OsiIAA1 is rapidly degraded by proteasome complex. The degradation of the protein was enhanced by the application of exogenous auxin. Also, the proteasome inhibitor MG132 stabilized the purified His6-OsiIAA1 protein to some extent in the cell-free extracts of rice coleoptiles. The OsiIAA1 protein harbors two nuclear localization signals (NLSs), one bipartite and the other resembling SV40 type NLS. Although both the NLSs were able to target the protein to the nucleus, the bipartite NLS was more effective. These studies indicate that nuclear localization of OsiIAA1 could be a prerequisite for its role in auxin signal transduction.
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PMID:Exogenous auxin enhances the degradation of a light down-regulated and nuclear-localized OsiIAA1, an Aux/IAA protein from rice, via proteasome. 1613 5

Auxin mediates numerous plant responses, some of which have been shown to require transcriptional regulation. One auxin response pathway, which depends on the relief of transcriptional repression, is mediated by TIR1 (transport inhibitor response protein 1). TIR1 is an auxin receptor and also a subunit of an SCF-type ubiquitin ligase. In the presence of a low concentration of auxin in the nucleus, members of the Aux/IAA family of transcriptional repressors bind to ARF proteins and inhibit the transcription of specific auxin response genes. Increased nuclear concentrations of auxin promote auxin binding to TIR1, causing the Aux/IAA proteins to associate with TIR1 and leading to their degradation by a proteasome-mediated pathway. This decreases the concentration of Aux/IAA proteins in the nucleus and thereby enables the expression of certain auxin response genes.
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PMID:Teaching resources. Model of the TIR1 pathway for auxin-mediated gene expression. 1647 40

Ubiquitin C-terminal hydrolases (UCHs) are a subset of de-ubiquitinating proteases that release covalently linked ubiquitin (Ub), and as such play essential roles in recycling Ub and reversing the action of Ub conjugation. We show here that two related Arabidopsis UCHs, UCH1, and UCH2, are important for shoot development. The UCH1 and 2 genes are ubiquitously expressed, with the corresponding proteins present in both the cytoplasm and nucleus. Unlike their animal and fungal counterparts, we found no evidence that the Arabidopsis UCH1 and 2 proteins stably associate with the 26S proteasome. Altering the levels of UCH1 and 2 has substantial effects on Arabidopsis shoot development, especially with respect to inflorescence architecture, with over-expression and double mutants enhancing and suppressing the outgrowth of cauline branches, respectively. Neither UCH1-over-expressing nor uch1-1 uch2-1 plants have detectably altered sensitivity to cytokinins or auxins individually, but exhibit an altered sensitivity to the ratio of the two hormones. UCH1-over-expressing plants show dramatically enhanced phenotypes when combined with auxin-insensitive mutants axr1-3 and axr2-1, suggesting that one or more aspects of auxin signaling are affected by this enzyme pair. Previous studies revealed that the ubiquitination and degradation of the AUX/IAA family of repressors is a key step in auxin signaling. Here, we show that turnover of a reporter fused to a representative AUX/IAA protein AXR3 is faster in the uch1-1 uch2-1 double mutant but slower in the UCH1 over-expression backgrounds. Taken together, our results indicate that de-ubiquitination helps to modify plant shoot architecture, possibly via its ability to directly or indirectly protect upstream target proteins involved in auxin/cytokinin signaling from Ub-mediated degradation.
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PMID:Ubiquitin C-terminal hydrolases 1 and 2 affect shoot architecture in Arabidopsis. 1755 14

Auxin-mediated gene expression is largely controlled through a family of DNA-binding proteins known as auxin response factors (ARF). Previous studies on the role of proteolytic regulation in auxin signaling have focused on degradation of their interacting partner, the Aux/IAA proteins. Aux/IAA family members with domain II sequences are rapidly degraded, show auxin-enhanced degradation rates, and interact with the related F-box proteins TIR1 and AFB1-3, which indicates that they are ubiquitylated by a CUL1-dependent E3 ligase. To date, limited data have been generated regarding degradation of ARFs. Here, we focus on the degradation rate of one ARF family member, Arabidopsis thaliana ARF1, and find that the half-lives of N-terminally HA-tagged ARF1 and C-terminally luciferase-tagged ARF1 are both approximately 3-4 h. This half-life appears to be conferred by a component of the middle region (MR), and degradation of the luciferase fusion with the MR is more rapid when the fusion includes an additional nuclear localization signal. ARF1 degradation is proteasome-dependent and rates are not altered in a CUL1 mutant background, suggesting that this ARF is targeted for proteasomal degradation via an alternative set of machinery to that used for Aux/IAA degradation. Consistent with this, exogenous indole acetic acid does not affect the degradation of ARF1. Given increasing evidence that the relative ratio of Aux/IAAs to ARFs rather than the absolute quantity within the cell appears to be the mode through which auxin signaling is modulated, this half-life is likely to be biologically relevant.
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PMID:Degradation of the auxin response factor ARF1. 1808 8

Many aspects of plant biology depend on the ubiquitin proteasome system for degradation of regulatory proteins. Ubiquitin E3 ligases confer substrate specificity in this pathway, and SCF-type ligases comprise a major class of E3s. SCF ligases have four subunits: SKP1, CUL1, RBX1, and an F-box protein for substrate recognition. The Aux/IAAs are a well-characterized family of SCF substrates in plants. Here, we report characterization of a mutant isolated from a genetic screen in Arabidopsis thaliana designed to identify plants defective in degradation of an Aux/IAA fusion protein, Aux/IAA1-luciferase (IAA1-LUC). This mutant exhibited fourfold slower IAA1-LUC degradation compared with the progenitor line, and seedlings displayed altered auxin responses. Experiments identified the mutant as an allele of CUL1, named cul1-7. The cul1-7 mutation affects the C terminus of the protein, results in reduced cul1-7 levels, and interferes with RBX1 interaction. cul1-7 seedlings are defective in degradation of an endogenous SCF substrate, Repressor of ga1-3 (RGA), and have altered responses to gibberellins. cul1-7 seedlings exhibit slower degradation of the light-labile red/far-red photoreceptor phytochrome A and are photomorphogenic in the dark. This mutation represents the first reported allele of CUL1 to directly affect subunit interactions at the CUL1 C terminus.
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PMID:Isolation and characterization of cul1-7, a recessive allele of CULLIN1 that disrupts SCF function at the C terminus of CUL1 in Arabidopsis thaliana. 1911 60

The auxins, plant hormones, play a crucial role in many aspects of plant development by regulating cell division, elongation and differentiation. Toyocamycin, a nucleoside-type antibiotic, was identified as auxin signaling inhibitor in a screen of microbial extracts for inhibition of the auxin-inducible reporter gene assay. Toyocamycin specifically inhibited auxin-responsive gene expression, but did not affect other hormone-inducible gene expression. Toyocamycin also blocked auxin-enhanced degradation of the Aux/IAA repressor modulated by the SCF(TIR1) ubiquitin-proteasome pathway without inhibiting proteolytic activity of proteasome. Furthermore, toyocamycin inhibited auxin-induced lateral root formation and epinastic growth of cotyledon in the Arabidopsis thaliana plant. This evidence suggested that toyocamycin would act on the ubiquitination process regulated by SCF(TIR1) machineries. To address the structural requirements for the specific activity of toyocamycin on auxin signaling, the structure-activity relationships of nine toyocamycin-related compounds, including sangivamycin and tubercidin, were investigated.
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PMID:Toyocamycin specifically inhibits auxin signaling mediated by SCFTIR1 pathway. 1917 57

The plant hormone auxin (indole-3-acetic acid or IAA) regulates plant development by inducing rapid cellular responses and changes in gene expression. Auxin promotes the degradation of Aux/IAA transcriptional repressors, thereby allowing auxin response factors (ARFs) to activate the transcription of auxin-responsive genes. Auxin enhances the binding of Aux/IAA proteins to the receptor TIR1, which is an F-box protein that is part of the E3 ubiquitin ligase complex SCF(TIR1). Binding of Aux/IAA proteins leads to degradation via the 26S proteasome, but evidence for SCF(TIR1)-mediated poly-ubiquitination of Aux/IAA proteins is lacking. Here we used an Arabidopsis cell suspension-based protoplast system to find evidence for SCF(TIR1)-mediated ubiquitination of the Aux/IAA proteins SHY2/IAA3 and BDL/IAA12. Each of these proteins showed a distinct abundance and repressor activity when expressed in this cell system. Moreover, the amount of endogenous TIR1 protein appeared to be rate-limiting for a proper auxin response measured by the co-transfected DR5::GUS reporter construct. Co-transfection with 35S::TIR1 led to auxin-dependent degradation, and excess of 35S::TIR1 even led to degradation of Aux/IAAs in the absence of auxin treatment. Expression of the mutant tir1-1 protein or the related F-box protein COI1, which is involved in jasmonate signaling, had no effect on Aux/IAA degradation. Our results show that SHY2/IAA3 and BDL/IAA12 are poly-ubiquitinated and degraded in response to increased auxin or TIR1 levels. In conclusion, our data provide experimental support for the model that SCF(TIR1)-dependent poly-ubiquitination of Aux/IAA proteins marks these proteins for degradation by the 26S proteasome, leading to activation of auxin-responsive gene expression.
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PMID:Auxin-induced, SCF(TIR1)-mediated poly-ubiquitination marks AUX/IAA proteins for degradation. 1930 53


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