Apple E3 ligase MdPUB23 mediates ubiquitin-dependent degradation of MdABI5 to delay ABA-triggered leaf senescence
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PROVIDER: S-EPMC10995623 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Drought stress conditions in soil or air hinder plant growth and development. Here, we report that the hot pepper (C apsicum a nnuum) RING type E3 Ligase 1 gene (CaREL1) is essential to the drought stress response. CaREL1 encodes a cytoplasmic- and nuclear-localized protein with E3 ligase activity. CaREL1 expression was induced by abscisic acid (ABA) and drought. CaREL1 contains a C3H2C3-type RING finger motif, which functions in ubiquitination of the target protein. We used CaREL1-silenced pepper plants and CaREL1-overexpressing (OX) transgenic Arabidopsis plants to evaluate the in vivo function of CaREL1 in response to drought stress and ABA treatment. CaREL1-silenced pepper plants displayed a drought-tolerant phenotype characterized by ABA hypersensitivity. In contrast, CaREL1-OX plants exhibited ABA hyposensitivity during the germination, seedling, and adult stages. In addition, plant growth was severely impaired under drought stress conditions, via a high level of transpirational water loss and decreased stomatal closure. Quantitative RT-PCR analyses revealed that ABA-related drought stress responsive genes were more weakly expressed in CaREL1-OX plants than in wild-type plants, indicating that CaREL1 functions in the drought stress response via the ABA-signalling pathway. Taken together, our results indicate that CaREL1 functions as a negative regulator of ABA-mediated drought stress tolerance.
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Project description:Toxoplasma gondii is an intracellular parasite that can activate the NLRP1 inflammasome leading to macrophage pyroptosis in Lewis rats, but the underlying mechanism is not well understood. In this study, we performed a genome-wide CRISPR screen and identified the dense granule proteins GRA35, GRA42, and GRA43 as the Toxoplasma effectors mediating cell death in Lewis rat macrophages. GRA35 localizes on the parasitophorous vacuole membrane, where it interacts with the host E3 ubiquitin ligase ITCH. Inhibition of proteasome activity or ITCH knockout prevented pyroptosis in Toxoplasma-infected Lewis rat macrophages, consistent with the "NLRP1 functional degradation model". However, there was no evidence that ITCH directly ubiquitinates or interacts with rat NLRP1. We also found that GRA35-ITCH interaction affected Toxoplasma fitness in IFNγ-activated human fibroblasts, likely due to ITCH's role in recruiting ubiquitin and the parasite-restriction factor RNF213 to the parasitophorous vacuole membrane. These findings identify a new role of host E3 ubiquitin ligase ITCH in mediating effector-triggered immunity, a critical concept that involves recognizing intracellular pathogens and initiating host innate immune responses.
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Project description:The endoplasmic reticulum resident thyroid hormone-activating type 2 deiodinase (D2) is inactivated by ubiquitination via the hedgehog-inducible WSB-1. Ubiquitinated D2 can then be subsequently taken up by the proteasomal system or be reactivated by USP-33/20-mediated deubiquitination. Given that heterologously expressed D2 accumulates in Saccharomyces cerevisiae lacking the E3 ligase Doa10, we tested whether the human Doa10 ortholog, TEB4, plays a role in D2 ubiquitination and degradation. In a setting of transient coexpression in HEK-293 cells, TEB4 and D2 could be coimmunoprecipitated, and additional TEB4 expression decreased D2 activity by approximately 50% (P < 0.05). A highly efficient TEB4 knockdown (>90% reduction in mRNA and protein levels) decreased D2 ubiquitination and increased D2 activity and protein levels by about fourfold. The other activating deiodinase, D1, or a truncated D2 molecule (Delta18-D2) that lacks a critical instability domain was not affected by TEB4 knockdown. Furthermore, TEB4 knockdown prolonged D2 activity half-life at least fourfold, even under conditions known to promote D2 ubiquitination. Neither exposure to 1 microM of the proteasomal inhibitor MG132 for 24 h nor RNA interference WSB-1 knockdown resulted in additive effects on D2 expression when combined with TEB4 knockdown. Similar results were obtained with MSTO-211 cells, which endogenously express D2, after TEB4 knockdown using a lentivirus-based transduction strategy. While TEB4 expression predominates in the hematopoietic lineage, both WSB-1 and TEB4 are coexpressed with D2 in a number of tissues and cell types, except the thyroid and brown adipose tissue, where TEB4 expression is minimal. We conclude that TEB4 interacts with and mediates loss of D2 activity, indicating that D2 ubiquitination and degradation can be tissue specific, depending on WSB-1 and TEB4 expression levels.
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Project description:BackgroundSubstance use disorder is a neurobiological disease characterized by episodes of relapse despite periods of withdrawal. It is thought that neuroadaptations in discrete brain areas of the reward pathway, including the nucleus accumbens, underlie these aberrant behaviors. The ubiquitin-proteasome system degrades proteins and has been shown to be involved in cocaine-induced plasticity, but the role of E3 ubiquitin ligases, which conjugate ubiquitin to substrates, is unknown. Here, we examined E3 ubiquitin-protein ligase SMURF1 (SMURF1) in neuroadaptations and relapse behavior during withdrawal following cocaine self-administration.MethodsSMURF1 and downstream targets ras homolog gene family, member A (RhoA), SMAD1/5, and Runt-related transcript factor 2 were examined using Western blotting (n = 9-11/group), quantitative polymerase chain reaction (n = 6-9/group), co-immunoprecipitation (n = 9-11/group), tandem ubiquitin binding entities affinity purification (n = 5-6/group), and quantitative chromatin immunoprecipitation (n = 3-6/group) (2 rats/sample). Viral-mediated gene transfer (n = 7-12/group) and intra-accumbal microinjections (n = 9-10/group) were used to examine causal roles of SMURF1 and substrate RhoA, respectively, in cue-induced cocaine seeking.ResultsSMURF1 protein expression was decreased, while SMURF1 substrates RhoA and SMAD1/5 were increased, in the nucleus accumbens on withdrawal day 7, but not on withdrawal day 1, following cocaine self-administration. Viral-mediated gene transfer of Smurf1 or constitutive activation of RhoA attenuated cue-induced cocaine seeking, while catalytically inactive Smurf1 enhanced cocaine seeking. Furthermore, SMURF1-regulated, SMAD1/5-associated transcription factor Runt-related transcript factor 2 displayed increased binding at promoter regions of genes previously associated with cocaine-induced plasticity.ConclusionsSMURF1 is a key mediator of neuroadaptations in the nucleus accumbens following cocaine exposure and mediates cue-induced cocaine seeking during withdrawal.
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Project description:The SPOP gene, which encodes an E3 ubiquitin ligase adaptor, is frequently mutated in a number of cancer types. However, the mechanisms by which SPOP functions as a tumor suppressor remain poorly understood. Here, we show that SPOP promotes senescence, an important tumor suppression mechanism, by targeting the SENP7 deSUMOylase for degradation. SPOP is upregulated during senescence. This correlates with ubiquitin-mediated degradation of SENP7, which promotes senescence by increasing HP1α sumoylation and the associated epigenetic gene silencing. Ectopic wild-type SPOP, but not its cancer-associated mutants, drives senescence. Conversely, SPOP knockdown overcomes senescence. These phenotypes correlate with ubiquitination and degradation of SENP7 and HP1α sumoylation, subcellular re-localization, and its associated gene silencing. Furthermore, SENP7 is expressed at higher levels in prostate tumor specimens with SPOP mutation (n = 13) compared to those with wild-type SPOP (n = 80). In summary, SPOP acts as a tumor suppressor by promoting senescence through degrading SENP7.
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