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

Ubiquitin C-terminal hydrolases (UCH) are deubiquitinating enzymes which hydrolyze C-terminal esters and amides of ubiquitin. Here we report the processing of a number of ubiquitin derivatives by two human UCH isozymes (isozymes L1 and L3) and find that these enzymes show little discrimination based on the P1' amino acid, except that proline is cleaved slowly. Ubiquitinyllysine derivatives linked by the alpha- or epsilon-amino group are hydrolyzed at identical rates. Isozyme-specific hydrolytic preferences are only evident when the leaving group is large. The ubiquitin gene products can be cotranslationally processed by one or both of these UCH isozymes, and purified UbCEP52 can be hydrolyzed by UCH isozyme L3. Binding of nucleic acid by UbCEP52 converts it to a form resistant to processing by these enzymes, apparently because of the formation of a larger, more tightly folded substrate. Consistent with this postulate is the observation that these enzymes do not hydrolyze large ubiquitin derivatives such as N epsilon-ubiquitinyl-cytochrome-c, N epsilon-K48polyubiquitinyl-lysozyme, or an N alpha-ubiquitinyl-beta-galactosidase fusion protein. Thus, these enzymes rapidly and preferentially cleave small leaving groups such as amino acids and oligopeptides from the C-terminus of ubiquitin, but not larger leaving groups such as proteins. These data suggest that the physiological role of UCH is to hydrolyze small adducts of ubiquitin and to generate free monomeric ubiquitin from ubiquitin proproteins, but not to deubiquitinate ubiquitin-protein conjugates or disassemble polyubiquitin chains.
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PMID:Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. 952 56

Plants respond to both biotic and abiotic stresses through a common signaling system to provide defense and protection against many adverse environments. Many genes/QTLs governing resistance to both biotic and abiotic stresses have been studied and mapped in rice. Sub1, a major QTL for submergence tolerance is collocated with a gene Gm1 for gall midge resistance on chromosome 9 (Region 1). Likewise a bigger region on chromosome 5 (Region 2) has a minor QTL for submergence tolerance collocated with genes for bacterial blight resistance. Utilizing the rice sequence and annotation data (TIGR) and rice genome annotation project database (RAP-DB), we wanted to know the kinds of genes underlying these two chromosomal regions where genes/QTL governing tolerance to both biotic and abiotic stresses are collocated. We also analyzed the pattern of distribution of these genes across the BAC/PAC clones spanning the region so that candidate genes can be short listed for a functional analysis. Genes known to have a role in submergence tolerance were present in both the regions. Region 1, had a unique transcription factor like trithorax protein, which is a positional candidate gene for submergence tolerance. Pyruvate decarboxylase (PDC) gene for alcohol fermentation and cation transporting ATPase c-terminal domain are likely candidates for submergence QTL in Region 2. Genes such as SKP1 and elicitor induced cytochrome p450 associated with tissue necrosis and insect resistance were found in region 1. Multiple copies of ORFs for signal transduction proteins, transcription factors, genes for systemic acquired resistance, Ubiquitin proteins and pathogen elicitor identification and degrading proteins were located as a cluster in Region 2, where bacterial blight resistance genes mapped. Validation of the data obtained from TIGR with other databases (RAP and KOME) confirmed our findings. The functional role of some of the significant candidate genes needs to be established. Allele/gene specific markers can then be designed for use in MAS thus enhancing durable tolerance/resistance faster.
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PMID:In silico insight into two rice chromosomal regions associated with submergence tolerance and resistance to bacterial leaf blight and gall midge. 1688 18

Ubiquitin carboxy terminal hydrolase-L1 (UCH-L1) belongs to the UCH proteases family that deubiquitinates ubiquitin-protein conjugates in the ubiquitin-proteasome system. Previous research showed that UCH-L1 was expressed in mouse retinal cells and testicular germ cells, and its function was associated with apoptosis. But it is still unclear whether UCH-L1 is concerned with apoptosis in tumor cells. In order to clarify the role of UCH-L1 in tumor cells, multi-drug resistance (MDR) human breast carcinoma cell line MCF7/Adr, that expresses relatively high UCH-L1, and its parental cell line MCF7, that expresses relatively low UCH-L1, were chosen for this study. We transfected pcDNA3.1-UCH-L1 plasmid and UCH-L1 siRNA into MCF7 and MCF7/Adr cells, respectively. Using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, western blot, Hoechst 33258 staining assay and flow cytometry, we found that over-expression of UCH-L1 in MCF7 cells induced apoptosis. On the other hand, silencing of UCH-L1 in MCF7/Adr cells led to the opposite effect. Moreover, to explore the mechanism underling these observations, we further investigated the expression of phospho-Akt and its downstream signal phospho-IkB-alpha and other signal molecules including Fas, Fas-L, Trail, DR4, DR5, Bax, cytochrome C, active caspase-3, phospho-p53, phospho-Mdm-2, Bcl-2, Bcl-xL, p21 and p27. The results indicated that the process of apoptosis triggered by UCH-L1 is, at least in part, probably through Phosphoinositide 3-kinase (PI3K)/Akt signal pathway. Our findings suggest that modulating the ubiquitination and deubiquitination pathway could be a novel method for tumor therapy.
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PMID:Over-expression of ubiquitin carboxy terminal hydrolase-L1 induces apoptosis in breast cancer cells. 1894 67