Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ubiquitin is a 76-residue protein which is highly conserved among eukaryotes. Sponge (Porifera) ubiquitin, isolated from Geodia cydonium, is encoded by a gene (termed GCUBI) with six repeats, GCUBI-1 to GCUBI-6. All repeat units encode the same protein (with one exception: GCUBI-4 encodes ubiquitin with a change of Leu to Val at position 71). On the nt level the sequences of the six repeats differ considerably. All changes (except in GCUBI-4) are silent substitutions, which do not affect the protein structure. However, there is one major difference between the repeats: Codons from both codon families (TCN and AGPy) are simultaneously used for the serine at position 65. Using this characteristic the repeats were divided into two groups: Group I: GCUBI-1,3 (TCT codon) and GCUBI-5 (TCC); Group II: GCUBI-2,4,6 (AGC codon). Mutational analysis suggests that the sponge polyubiquitin gene evolved from an ancestral monoubiquitin gene by gene duplication and successive tandem duplications. The ancestral monoubiquitin gene most probably coded for threonine (ACC) at position 65. The first event, duplication of the monoubiquitin gene, happened some 110 million years ago. Since sponges from the genus Geodia are known from the Cretaceous (145 million) to recent time, it is very likely that all events in the evolution of polyubiquitin gene occurred in the same genus. Alignment data of the "consensus" ubiquitin nt sequences of different animals (man to protozoa) reflect very well the established phylogenetic relationships of the chosen organisms and show that the sponge ubiquitin gene branched off first from the multicellular organisms.
J Mol Evol 1994 Oct
PMID:Phylogenetic relationship of ubiquitin repeats in the polyubiquitin gene from the marine sponge Geodia cydonium. 796 67

Ubiquitin genes provide a model for studying the effects of concerted evolution on the evolution of a family of short repeated sequences. Previous work has demonstrated the occurrence of within-locus concerted evolution and raised the question of the effectiveness of between-locus concerted evolution for ubiquitin repeats. In this study comparative analysis of additional nucleotide sequences of ubiquitin tandem repeats provides further details of within-locus concerted evolution. Moreover, the availability of multiple polyubiquitin loci and ubiquitin fusion loci within a species makes possible the detection of between-locus concerted evolution. These data indicate that concerted evolution is an effective force for homogenizing repeats between, as well as within, loci.
Mol Phylogenet Evol 1993 Dec
PMID:Ubiquitins revisited: further examples of within- and between-locus concerted evolution. 804 84

The FAU gene (FBR-MuSV associated ubiquitously expressed gene) encodes the ribosomal protein S30 fused with a Ubiquitin-like molecule. The FAU gene is expressed in a wide range of tissues, is evolutionarily conserved, and has putative tumour suppressor activity in vitro. The human FAU gene maps to the long arm of chromosome 11 band q13, close to the PYGM locus. This locus is tightly linked to the Multiple Endocrine Neoplasia type 1 (MEN1) locus. The FAU gene properties, together with its chromosomal localisation on 11q13, make it a candidate gene for MEN1. To test this hypothesis we screened 33 unrelated patients with MEN1 for constitutional genetic alterations in the FAU gene by Southern blot analysis, denaturing gradient gel electrophoresis (DGGE) and in two cases complemented by DNA sequencing to confirm the DGGE data. Furthermore, 10 parathyroid and pancreatic tumours from MEN1 patients and 15 each of sporadic parathyroid and pituitary tumours were similarly examined. In addition, we studied the expression of the FAU gene at the RNA level in 9 MEN1-associated tumours by Northern blot analysis. No FAU gene anomalies could be demonstrated by any of these techniques. We conclude that FAU is not likely to be the MEN1 tumour suppressor gene.
Hum Mol Genet 1993 Apr
PMID:Exclusion of FAU as the multiple endocrine neoplasia type 1 (MEN1) gene. 809 2

Ubiquitin is an omnipresent protein found in all eukaryotes so far analysed. It is involved in several important processes, including protein turnover, chromosome structure and stress response. Parsley (Petroselinum crispum) contains at least two active polyubiquitin (ubi4) genes encoding hexameric precursor proteins. The deduced amino acid sequences of the ubiquitin monomers are identical to one another and to ubiquitin sequences from several other plant species. Analysis of the promoter region of one ubi4 gene revealed putative regulatory elements. In parsley plants, the ubi4 mRNAs were the predominant ubiquitin mRNAs and were present at comparable levels in all plant organs tested. In cultured parsley cells, high levels of ubiquitin gene expression remained unaffected by heat shock, elicitor or light treatment.
Plant Mol Biol 1993 Feb
PMID:Polyubiquitin gene expression and structural properties of the ubi4-2 gene in Petroselinum crispum. 838 52

A dominant insertional P-element mutation enhances position-effect variegation in Drosophila melanogaster. The mutation is homozygous, viable, and fertile and maps at 64E on the third chromosome. The corresponding gene was cloned by transposon tagging. Insertion of the transposon upstream of the open reading frame correlates with a strong reduction of transcript level. A transgene was constructed with the cDNA and found to have the effect opposite from that of the mutation, namely, to suppress variegation. Sequencing of the cDNA reveals a large open reading frame encoding a putative ubiquitin-specific protease (Ubp). Ubiquitin marks various proteins, frequently for proteasome-dependent degradation. Ubps can cleave the ubiquitin part from these proteins. We discuss the link established here between a deubiquitinating enzyme and epigenetic silencing processes.
Mol Cell Biol 1996 Oct
PMID:The dose of a putative ubiquitin-specific protease affects position-effect variegation in Drosophila melanogaster. 881 85

Ubiquitin gene expression following transient forebrain ischemia in the rat was analyzed by three probes which were specific for UbC, UbB and UbS30 mRNA. According to the in situ hybridization studies, each type of ubiquitin gene expression decreased at 30 min of reperfusion following 20 min of forebrain ischemia, thereafter increased, and then reached a peak at 4-6 h, both in the cortex and hippocampus. These changes returned to the control level after 24-48 h of recirculation. Among the three ubiquitin transcripts, changes in UbC expression were more marked in the hippocampus, and persistent expression of UbC transcripts in the CA1 and CA3 regions was observed at 24 h of reperfusion. With dot-blot analysis, significant increases in the UbC transcripts were noted at 4 h of reperfusion in the hippocampus, and at 6 h in the cortex following 20 min of ischemia. These results suggest that changes in UbC expression might be a good indicator of ischemic stress.
Brain Res Mol Brain Res 1996 Mar
PMID:Ubiquitin gene expression following transient forebrain ischemia. 896 46

Levels of the tumor suppressor protein p53 are normally quite low due in part to its short half-life. p53 levels increase in cells exposed to DNA-damaging agents, such as radiation, and this increase is thought to be responsible for the radiation-induced G1 cell cycle arrest or delay. The mechanisms by which radiation causes an increase in p53 are currently unknown. The purpose of this study was to compare the effects of gamma and UV radiation on the stability and ubiquitination of p53 in vivo. Ubiquitin-p53 conjugates could be detected in nonirradiated and gamma-irradiated cells but not in cells which were UV treated, despite the fact that both treatments resulted in the stabilization of the p53 protein. These results demonstrate that UV and gamma radiation have different effects on ubiquitinated p53 and suggest that the UV-induced stabilization of p53 results from a loss of p53 ubiquitination. Ubiquitinated forms of p21, an inhibitor of cyclin-dependent kinases, were detected in vivo, demonstrating that p21 is also a target for degradation by the ubiquitin-dependent proteolytic pathway. However, UV and gamma radiation had no effect on the stability or in vivo ubiquitination of p21, indicating that the radiation effects on p53 are specific.
Mol Cell Biol 1997 Jan
PMID:Ubiquitination of p53 and p21 is differentially affected by ionizing and UV radiation. 897 16

Ubiquitin-mediated proteolysis is involved in the turnover of many short-lived regulatory proteins. This pathway leads to the covalent attachment of one or more multiubiquitin chains to target substrates which are then degraded by the 26S multicatalytic proteasome complex. Multiple classes of regulatory enzymes have been identified that mediate either ubiquitin conjugation or ubiquitin deconjugation from target substrates. Timed destruction of cellular regulators by the ubiquitin-proteasome pathway plays a critical role in ensuring normal cellular processes. This review provides multiple examples of key growth regulatory proteins whose levels are regulated by ubiquitin-mediated proteolysis. Pharmacological intervention which alters the half-lives of these cellular proteins may have wide therapeutic potential. Specifically, prevention of p53 ubiquitination (and subsequent degradation) in human papilloma virus positive tumors, and perhaps all tumors retaining wild-type p53 but lacking the retinoblastoma gene function, should lead to programmed cell death. Specific inhibitors of p27 and cyclin B ubiquitination are predicted to be potent antiproliferative agents. Inhibitors of IkappaB ubiquitination should prevent NFkappaB activation and may have utility in a variety of autoimmune and inflammatory conditions. Finally, we present a case for deubiquitination enzymes as novel, potential drug targets.
J Mol Med (Berl) 1997 Jan
PMID:The ubiquitin-mediated proteolytic pathway as a therapeutic area. 902 Mar 79

Ubiquitin, a heat-shock protein highly expressed during spermatogenesis, plays an essential role in the differentiation of the germinal cells, particularly in the structural changes of chromatin taking place at the end of the process. To shed light on the mechanisms that modulate transcriptional activity of the heat-shock inducible polyubiquitin gene UbI during spermatogenesis and stabilize the message when transcription is not longer active, we have compared the characteristics of UbI transcripts in mature and immature testes and somatic cells. In mature chicken testes, transcription starts at a site placed closer to the heat-shock promoters than in somatic tissues. This site is upstream from the TATA box used in somatic cells. In addition, UbI transcript undergoes an alternative splicing that produces a longer 5' untranslated region in mature testis. These findings may provide a basis for the observed increase in expression of UbI in mature chicken testes and for the stability of the message when transcription ceases at the end of spermatogenesis.
Mol Reprod Dev 1997 Apr
PMID:Heat-shock inducible polyubiquitin gene UbI undergoes alternative initiation and alternative splicing in mature chicken testes. 909 93

We have investigated three aspects of nucleotide usage by the 26S proteasome and its regulatory complex (RC). Both particles hydrolyze the four major ribonucleotides, but ATP and CTP have substantially lower Kms for hydrolysis than do GTP and UTP. The Km for ATP hydrolysis is 15 microm for the 26S proteasome and 30 microm for the regulatory complex. Formation of the 26S proteasome from the RC and the 20S proteasome requires about 5 microm ATP. Although measurable degradation of Ubiquitin(Ub)-lysozyme conjugates occurs in the presence of CTP, GTP, and UTP, the best nucleotide for Ub-conjugate degradation by the 26S proteasome is ATP, with an estimated Km of 12 microm. In summary, our studies show that micromolar concentrations of ATP are sufficient for several 26S proteasome activities.
Mol Biol Rep 1997 Mar
PMID:Effects of nucleotides on assembly of the 26S proteasome and degradation of ubiquitin conjugates. 922 75


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