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)

COP1 (for CONSTITUTIVELY PHOTOMORPHOGENIC1) and the four partially redundant SPA (for SUPPRESSOR OF PHYA) proteins work in concert to repress photomorphogenesis in Arabidopsis thaliana by targeting key transcription factors and phytochrome A for degradation via the 26S proteasome. Here, we report a detailed biochemical characterization of the SPA-COP1 complexes. The four endogenous SPA proteins can form stable complexes with COP1 in vivo regardless of light conditions but exhibit distinct expression profiles in different tissues and light conditions. The SPA proteins can self-associate or interact with each other, forming a heterogeneous group of SPA-COP1 complexes in which the exact SPA protein compositions vary depending on the abundance of individual SPA proteins. The four SPA proteins could be divided into two functional groups depending on their interaction affinities, their regulation of ELONGATED HYPOCOTYL5 degradation, and their opposite effects on COP1 protein accumulation. Loss-of-function mutations in a predominant SPA protein may cause a significant reduction in the overall SPA-COP1 E3 ligase activity, resulting in a partial constitutive photomorphogenic phenotype. This study thus provides an in-depth biochemical view of the SPA-COP1 E3 ligase complexes and offers new insights into the molecular basis for their distinct roles in the light control of plant development.
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PMID:Biochemical characterization of Arabidopsis complexes containing CONSTITUTIVELY PHOTOMORPHOGENIC1 and SUPPRESSOR OF PHYA proteins in light control of plant development. 1881 98

COP1 is a Ring-Finger E3 ubiquitin ligase that is involved in plant development, mammalian cell survival, growth, and metabolism. Here we report that COP1, whose expression is enhanced by insulin, regulates FoxO1 protein stability. We found that in Fao hepatoma cells, ectopic expression of COP1 decreased, whereas knockdown of COP1 expression increased the level of endogenous FoxO1 protein without impacting other factors such as C/EBPalpha and CREB (cAMP-response element-binding protein). We further showed that COP1 binds FoxO1, enhances its ubiquitination, and promotes its degradation via the ubiquitin-proteasome pathway. To determine the biological significance of COP1-mediated FoxO1 protein degradation, we have examined the impact of COP1 on FoxO1-mediated gene expression and found that COP1 suppressed FoxO1 reporter gene as well as FoxO1 target genes such as glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, two key targets for FoxO1 in the regulation of gluconeogenesis, with corresponding changes of hepatic glucose production in Fao cells. We suggest that by functioning as a FoxO1 E3 ligase, COP1 may play a role in the regulation of hepatic glucose metabolism.
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PMID:COP1 functions as a FoxO1 ubiquitin E3 ligase to regulate FoxO1-mediated gene expression. 1881 34

Arabidopsis GBF1/ZBF2 is a bZIP transcription factor that plays dual but opposite regulatory roles in cryptochrome-mediated blue light signaling. Here, we show the genetic and molecular interrelation of GBF1 with two well characterized negative regulators of light signaling, COP1 and SPA1, in photomorphogenic growth and light-regulated gene expression. Our results further reveal that GBF1 protein is less abundant in the dark-grown seedlings and is degraded by a proteasome-mediated pathway independent of COP1 and SPA1. Furthermore, COP1 physically interacts with GBF1 and is required for the optimum accumulation of GBF1 protein in light-grown seedlings. Taken together, this study provides a mechanistic view of concerted function of three important regulators in Arabidopsis seedling development.
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PMID:GBF1, a transcription factor of blue light signaling in Arabidopsis, is degraded in the dark by a proteasome-mediated pathway independent of COP1 and SPA1. 1893 Sep 26

The COP9 signalosome (CSN) complex is highly conserved from yeast to human. Although the plant CSN was first identified as a negative regulator of photomorphogenesis, the mammalian CSN is linked to different biological responses such as checkpoint control, signal transduction, development and the cell cycle. Frequent over-expression of the CSN subunit in a variety of human cancers suggests its involvement in cell transformation and tumorigenesis. The best-known biochemical function associated with the CSN is the control of protein stability via the ubiquitin-proteasome system through regulation of cullin-RING-E3 ubiquitin ligase activity by deneddylation, by controlling the activity of COP1 E3 ligase, or by counteracting ubiquitin-mediated degradation through a CSN-associated deubiquitinating enzyme. In addition to affecting the stability of transcription factors, the CSN may regulate gene transcription by directly associating with chromatin. This review summarizes recent findings and discusses the physiological role and the cellular function of the mammalian CSN in terms of the regulation of cell proliferation.
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PMID:Mammalian COP9 signalosome. 1984 19

The ubiquitination proteasome pathway has been demonstrated to regulate all plant developmental and signaling processes. E3 ligase/substrate-specific interactions and ubiquitination play important roles in this pathway. However, due to technical limitations only a few instances of E3 ligase-substrate binding and protein ubiquitination in plants have been directly evidenced. An efficient in vivo and in vitro ubiquitination assay was developed for analysis of protein ubiquitination reactions by agroinfiltration expression of both substrates and E3 ligases in Nicotiana benthamiana. Using a detailed analysis of the well-known E3 ligase COP1 and its substrate HY5, we demonstrated that this assay allows for fast and reliable detection of the specific interaction between the substrate and the E3 ligase, as well as the effects of MG132 and substrate ubiquitination and degradation. We were able to differentiate between the original and ubiquitinated forms of the substrate in vivo with antibodies to ubiquitin or to the target protein. We also demonstrated that the substrate and E3 ligase proteins expressed by agroinfiltration can be applied to analyze ubiquitination in in vivo or in vitro reactions. In addition, we optimized the conditions for different types of substrate and E3 ligase expression by supplementation with the gene-silencing suppressor p19 and by time-courses of sample collection. Finally, by testing different protein extraction buffers, we found that different types of buffer should be used for different ubiquitination analyses. This method should be adaptable to other protein modification studies.
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PMID:An efficient system to detect protein ubiquitination by agroinfiltration in Nicotiana benthamiana. 2001 64

MDM2, Pirh2 and COP1 are important E3 ubiquitin ligases, which directly interact with p53 and target p53 for proteasome-mediated degradation. MDMX, the MDM2 homologous protein, inhibits p53-mediated transcription activity. The interplay between MDM2, MDMX, Pirh2 and COP1 has not been reported, except the interaction between MDM2 and MDMX. Here, we reported that there were interactions between these four proteins independently of p53. The protein levels of MDM2, MDMX, Pirh2 and COP1 changed when any two of them were co-transfected. Our data also showed that the integrity of MDM2 RING finger domain was crucial for its ability to elevate the protein levels of COP1 and Pirh2. Any two of these four proteins could inhibit p53-mediated transcriptional activity synergistically. Furthermore, COP1 inhibited MDM2 self-ubiquitination and interfered with MDMX ubiquitination by MDM2. Our results suggest that MDM2, MDMX, Pirh2 and COP1 might inhibit p53 activity synergistically in vivo.
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PMID:Interplay between MDM2, MDMX, Pirh2 and COP1: the negative regulators of p53. 2033 47

Light harvested by plants is essential for the survival of most life forms. This light perception ability requires the activities of proteins termed photoreceptors. We report a function for photoreceptors in mediating resistance (R) protein-derived plant defense. The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are required for the stability of the R protein HRT, and thereby resistance to Turnip Crinkle virus (TCV). Exposure to darkness or blue-light induces degradation of CRY2, and in turn HRT, resulting in susceptibility. Overexpression of HRT can compensate for the absence of PHOT2 but not CRY2. HRT does not directly associate with either CRY2 or PHOT2 but does bind the CRY2-/PHOT2-interacting E3 ubiquitin ligase, COP1. Application of the proteasome inhibitor, MG132, prevents blue-light-dependent degradation of HRT, consequently these plants show resistance to TCV under blue-light. We propose that CRY2/PHOT2 negatively regulate the proteasome-mediated degradation of HRT, likely via COP1, and blue-light relieves this repression resulting in HRT degradation.
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PMID:Cryptochrome 2 and phototropin 2 regulate resistance protein-mediated viral defense by negatively regulating an E3 ubiquitin ligase. 2062 51

This light-perciving ability of plants requires the activities of proteins termed photoreceptors. In addition to various growth and developmental processes, light also plays a role in plant defense against pathogens and is required for activation of several defense genes and regulation of the cell death response. However, the molecular or biochemical basis of light modulated regulation of defense signaling is largely unclear. We demonstrate a direct role for blue-light photoreceptors in resistance (R) protein-mediated plant defense against Turnip Crinkle Virus (TCV) in Arabidopsis. The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are specifically required for maintaining the stability of the R protein HRT, and thereby resistance to TCV. Exogenous application of the phytohormone salicylic acid elevates HRT levels in phot2 but not in cry2 background. These data indicate that CRY2 and PHOT2 function distinctly in maintaining post-transcriptional stability of HRT. HRT-mediated resistance is also dependent on CRY1 and PHOT1 proteins, but these do not contribute to the stability of HRT. HRT interacts with the CRY2/PHOT2-interacting protein COP1, a E3 ubiquitin ligase. Exogenous application of a proteasome inhibitor prevents blue-light-dependent degradation of HRT, suggesting that HRT is degraded via the 26S proteasome. These and the fact that PHOT2 interacts directly with the R protein RPS2 suggest that blue-light photoreceptors might be involved in regulation and/or signaling mediated by several R proteins.
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PMID:Blue light photoreceptors are required for the stability and function of a resistance protein mediating viral defense in Arabidopsis. 2105 10

Light regulates multiple aspects of growth and development in plants. Transcriptomic changes govern the expression of signaling molecules with the perception of light. Also, the 26S proteasome regulates the accumulation of positive and negative regulators for optimal growth of Arabidopsis (Arabidopsis thaliana) in the dark, light, or light/dark cycles. BBX22, whose induction is both light regulated and HY5 dependent, is a positive regulator of deetiolation in Arabidopsis. We found that during skotomorphogenesis, the expression of BBX22 needs to be tightly regulated at both transcriptional and posttranslational levels. During photomorphogenesis, the expression of BBX22 transiently accumulates to execute its roles as a positive regulator. BBX22 protein accumulates to a higher level under short-day conditions and functions to inhibit hypocotyl elongation. The proteasome-dependent degradation of BBX22 protein is tightly controlled even in plants overexpressing BBX22. An analysis of BBX22 degradation kinetics shows that the protein has a short half-life under both dark and light conditions. COP1 mediates the degradation of BBX22 in the dark. Although dispensable in the dark, HY5 contributes to the degradation of BBX22 in the light. The constitutive photomorphogenic development of the cop1 mutant is enhanced in cop1BBX22ox plants, which show a short hypocotyl, high anthocyanin accumulation, and expression of light-responsive genes. Exaggerated light responsiveness is also observed in cop1BBX22ox seedlings grown under short-day conditions. Therefore, the proper accumulation of BBX22 is crucial for plants to maintain optimal growth when grown in the dark as well as to respond to seasonal changes in daylength.
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PMID:COP1-mediated degradation of BBX22/LZF1 optimizes seedling development in Arabidopsis. 2142 83

COP1 and DET1 are among the first repressors of photomorphogenesis to be identified, more than 20 years ago. Discovery of these repressors as conserved regulators of the ubiquitin-proteasome system has established protein degradation as a central theme in light signal transduction. COP1 is a RING E3 ubiquitin ligase that targets key regulators for degradation, and DET1 complexes with COP10 and DDB1, which is proposed to aid in COP1-mediated degradation. Recent studies have strengthened the role of COP1 as a major signaling center. DET1 is also emerging as a chromatin regulator in repressing gene expression. Here, we review current understanding on COP1 and DET1, with a focus on their role as part of two distinct, multimeric CUL4-based E3 ligases.
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PMID:The photomorphogenic repressors COP1 and DET1: 20 years later. 2270 57


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