Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P62988 (Ubiquitin)
4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ubiquitin/proteasome-mediated protein degradation controls various developmental pathways in eukaryotes. Cullin-containing complexes are both versatile and abundant groups of RING family ubiquitin E3 ligases, whose activities are subject to control by RUB/Nedd8 (for related to ubiquitin/neural precursor cell-expressed developmentally downregulated 8) modification of their cullin subunits. Here, we report the identification of an Arabidopsis thaliana counterpart of human CAND1 (cullin-associated and neddylation-dissociated) and demonstrate that it can preferentially interact with unmodified CUL1. The Arabidopsis cand1-1 null mutant displays distinct phenotypes, including late flowering, aerial rosettes, floral organ defects, low fertility, dwarfism, loss of apical dominance, and altered responses to multiple plant hormones. Molecular analyses show that many of these defects are because of compromised activity of CUL1-containing ubiquitin E3 ligases, indicating that CAND1 is required for their optimal activity. Furthermore, the cand1-1 mutant displays a partial constitutive photomorphogenic phenotype and has defects in HY5 degradation in the absence of light, a process mediated by a different RING family E3, COP1. Thus, our data provides genetic support for a critical role of CAND1 in regulating various ubiquitin E3 ligases and their targeted cellular and developmental pathways.
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PMID:Arabidopsis CAND1, an unmodified CUL1-interacting protein, is involved in multiple developmental pathways controlled by ubiquitin/proteasome-mediated protein Degradation. 1520 91

The E3 ubiquitin ligase CRL4COP1/DET1 is active in the absence of ERK signaling, modifying the transcription factors ETV1, ETV4, ETV5, and c-JUN with polyubiquitin that targets them for proteasomal degradation. Here we show that this posttranslational regulatory mechanism is active in neurons, with ETV5 and c-JUN accumulating within minutes of ERK activation. Mice with constitutive photomorphogenesis 1 (Cop1) deleted in neural stem cells showed abnormally elevated expression of ETV1, ETV4, ETV5, and c-JUN in the developing brain and spinal cord. Expression of c-JUN target genes Vimentin and Gfap was increased, whereas ETV5 and c-JUN both contributed to an expanded number of cells expressing genes associated with gliogenesis, including Olig1, Olig2, and Sox10. The mice had subtle morphological abnormalities in the cerebral cortex, hippocampus, and cerebellum by embryonic day 18 and died soon after birth. Elevated c-JUN, ETV5, and ETV1 contributed to the perinatal lethality, as several Cop1-deficient mice also lacking c-Jun and Etv5, or lacking Etv5 and heterozygous for Etv1, were viable.
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PMID:Ubiquitin ligase COP1 coordinates transcriptional programs that control cell type specification in the developing mouse brain. 3032 23

Light is a key environmental factors affecting anthocyanin accumulation in plants. Ubiquitin E3 ligase COP1 has been proved to be a negative regulator involved in light-regulated plant development process, whereas the function and expression specificity of COP1 in anthocyanin biosynthesis in sweet cherry remains unclear. In the present study, we identified a COP1 in sweet cherry, named PacCOP1, it exhibited apparent different expression patterns in red-colored 'Hongdeng' and bi-colored 'Satonishiki', with increasing trend largely in 'Satonishiki', but decreasing trend in 'Hongdeng' after veraison, which was contrary to their variation tendency of anthocyanin content. While the expression abundance of anthocyanin biosynthesis related genes were largely increased after veraison, in accordance with anthocyanin content. Correlation analysis proved that the expression of PacCOP1 was negative correlated with the major genes on anthocyanin accumulation in 'Hongdeng' and 'Satonishiki' fruit, in especial PacDFR, PacANS, PacMYBA and PacbHLH33. Furthermore, over-expression of PacCOP1 in Arabidopsis displayed increased COP1 transcript level with negligible pigmentation and corresponding lower expression level of AtPAP1, AtDFR, AtLDOX, and AtUFGT. These results revealed the negative regular role of PacCOP1 in anthocyanin biosynthesis by repressing the PacMYBA transcription level, followed by down-regulating the structural genes expression abundance, eventually leading to attenuated anthocyanin accumulation in fruits.
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PMID:PacCOP1 negatively regulates anthocyanin biosynthesis in sweet cherry (Prunus avium L.). 3192 87