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)

The ubiquitin-like protein RUB1 is conjugated to target proteins by a mechanism similar to that of ubiquitin conjugation. Genetic studies in Arabidopsis thaliana have implicated the RUB-conjugation pathway in auxin response. The first step in the pathway is RUB activation by a bipartite enzyme composed of the AXR1 and ECR1 proteins. Ubiquitin activation is an ATP-dependent process that involves the formation of an AMP-ubiquitin intermediate. Here we show that RUB activation by AXR1-ECR1 also involves formation of an AMP-RUB intermediate and that this reaction is catalyzed by the ECR1 subunit alone. In addition, we identified an Arabidopsis protein called RCE1 that is a likely RUB-conjugating enzyme. RCE1 works together with AXR1-ECR1 to promote formation of a stable RUB conjugate with the Arabidopsis cullin AtCUL1 in vitro. Using a tagged version of RUB1, we show that this modification occurs in vivo. Because AtCUL1 is a component of the ubiquitin protein ligase SCF(TIR1), a complex that also functions in auxin response, we propose that RUB modification of AtCUL1 is important for auxin response.
 ...
PMID:The Arabidopsis cullin AtCUL1 is modified by the ubiquitin-related protein RUB1. 1061 86

Selective protein degradation by the ubiquitin-proteosome pathway has recently emerged as a powerful regulatory mechanism in a wide variety of cellular processes. Ubiquitin conjugation requires the sequential activity of three enzymes or protein complexes called the ubiquitin-activating enzyme (E1), the ubiquitin-conjugating enzyme (E2), and the ubiquitin-protein ligase (E3). In most eukaryotes, there are a small number of similar E1 isoforms without apparent functional specificity. The specific selection of target proteins is accomplished by the E2 and E3 proteins. One of the best-characterized families of E3s are the SCF complexes. The SCF is composed of a cullin (Cdc53), SKP1, RBX1 and one member of a large family of proteins called F-box proteins. The function of the F-box protein is to interact with target proteins. In some cases, the stability of the F-box protein may regulate activity of the SCF complex. In addition, post-translational modification of the cullin subunit by the ubiquitin-like protein RUB/NEDD8 appears to regulate SCF function. In plants, the SCF has so far been implicated in floral development, circadian clock, and response to the plant growth regulators auxin and jasmonic acid.
 ...
PMID:F-box proteins and protein degradation: an emerging theme in cellular regulation. 1111 56

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.
 ...
PMID:Arabidopsis CAND1, an unmodified CUL1-interacting protein, is involved in multiple developmental pathways controlled by ubiquitin/proteasome-mediated protein Degradation. 1520 91

The COP9 signalosome (CSN) is an evolutionarily conserved multisubunit protein complex involved in a variety of signaling and developmental processes through the regulation of protein ubiquitination and degradation. A known biochemical role attributed to CSN is a metalloprotease activity responsible for the derubylation of cullins, core components for several types of ubiquitin E3 ligases. The CSN's derubylation catalytic center resides in its subunit 5, which in Arabidopsis thaliana is encoded by two homologous genes, CSN5A and CSN5B. Here, we show that CSN5A and CSN5B subunits are assembled into distinct CSN complexes in vivo, which are present in drastically different abundances, with CSN(CSN5A) appearing to be the dominant one. Transgenic CSN5A and CSN5B proteins carrying a collection of single mutations in or surrounding the metalloprotease catalytic center are properly assembled into CSN complexes, but only mutations in CSN5A result in a pleiotropic dominant negative phenotype. The extent of phenotypic effects caused by mutations in CSN5A is reflected at the molecular level by impairment in Cullin1 derubylation. These results reveal that three key metal binding residues as well as two other amino acids outside the catalytic center play important roles in CSN derubylation activity. Taken together, our data provide physiological evidence on a positive role of CSN in the regulation of Arabidopsis SCF (for Skp1-Cullin-F-box) E3 ligases through RUB (for Related to Ubiquitin) deconjugation and highlight the unequal role that CSN(CSN5A) and CSN(CSN5B) play in controlling the cellular derubylation of cullins. The initial characterization of CSN5A and CSN5B insertion mutants further supports these findings and provides genetic evidence on their unequal role in plant development.
 ...
PMID:The Arabidopsis CSN5A and CSN5B subunits are present in distinct COP9 signalosome complexes, and mutations in their JAMM domains exhibit differential dominant negative effects on development. 1548 99

Regulated protein degradation contributes to plant development by mediating signaling events in many hormone, light, and developmental pathways. Ubiquitin ligases recognize and ubiquitinate target proteins for subsequent degradation by the 26S proteasome. The multisubunit SCF is the best-studied class of ubiquitin ligases in Arabidopsis (Arabidopsis thaliana). However, the extent of SCF participation in signaling networks is unclear. SCFs are composed of four subunits: CULLIN 1 (CUL1), ASK, RBX1, and an F-box protein. Null mutations in CUL1 are embryo lethal, limiting insight into the role of CUL1 and SCFs in later stages of development. Here, we describe a viable and fertile weak allele of CUL1, called cul1-6. cul1-6 plants have defects in seedling and adult morphology. In addition to reduced auxin sensitivity, cul1-6 seedlings are hyposensitive to ethylene, red, and blue light conditions. An analysis of protein interactions with the cul1-6 gene product suggests that both RUB (related to ubiquitin) modification and interaction with the SCF regulatory protein CAND1 (cullin associated and neddylation dissociated) are disrupted. These findings suggest that the morphological defects observed in cul1-6 plants are caused by defective SCF complex formation. Characterization of weak cul1 mutants provides insight into the role of SCFs throughout plant growth and development.
 ...
PMID:A new CULLIN 1 mutant has altered responses to hormones and light in Arabidopsis. 1715 85

The ubiquitin/26S proteasome pathway largely mediates selective proteolysis in the nucleus and cytosol. This pathway catalyzes covalent attachment of ubiquitin (UBQ) to substrate proteins in an E1-E2-E3 cascade. Ubiquitin E3 ligases interact with substrates to catalyze UBQ transfer from E2 to substrate. Within the E3 ligase superfamily, cullin RING ligases (CRLs) are significant in plants because they are linked to hormonal signaling, developmental programs, and environmental responses. Thus, knowledge of CRL regulation is required for a complete understanding of these processes. A major mechanism modulating CRL activity is modification of the cullin subunit by RUB (RELATED TO UBIQUITIN), a ubiquitin-like protein, and demodification by the COP9 signalosome (CSN). CULLIN-ASSOCIATED NEDD8-DISSOCIATED 1 (CAND1) interacts with CRLs, affecting both rubylation and derubylation. Described here are the pathways, regulation, and biological function of rubylation and derubylation, as well as future directions and outstanding questions.
 ...
PMID:Regulation of cullin RING ligases. 1844 5