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-dependent selective protein degradation serves to eliminate abnormal proteins and provides controlled short half-lives to certain cellular proteins, including proteins of regulatory function such as phytochrome, yeast MAT alpha 2 repressor, p53 and cyclin. Moreover, ubiquitin-dependent proteolysis is thought to play an essential role during development and in programmed cell death. We have cloned a gene from Drosophila melanogaster, UbcD1, coding for a protein with striking sequence similarity to the yeast ubiquitin-conjugating enzymes UBC4 and UBC5. These closely related yeast enzymes are known to be central components of a major proteolytic pathway of Saccharomyces cerevisiae. By doing a precise open reading frame replacement in the yeast genome we could show that the Drosophila UbcD1 enzyme can functionally substitute for yeast UBC4. UbcD1 driven by the UBC4 promoter rescues growth defects and temperature sensitivity of yeast ubc4 ubc5 double mutant cells. Moreover, expression of UbcD1 restores proteolysis proficiency in the ubc4 ubc5 double mutant, indicating that the Drosophila enzyme also mediates protein degradation. This structural and functional conservation suggests that the UbcD1-UBC4-UBC5 class of enzymes defines a major proteolytic pathway in probably all eukaryotes.
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PMID:Drosophila UbcD1 encodes a highly conserved ubiquitin-conjugating enzyme involved in selective protein degradation. 131 Sep 35

LORIEN (encoding a protein that contains a SP-RING/Miz zinc-finger motif present in a group of proteins involved in the Small Ubiquitin-related Modifier -SUMO- conjugation pathway) and MAT2 (encoding the methionine adenosyltransferase -MAT-) genes are arranged as two alternating copies in a head-to-tail configuration, with the LORIEN gene as the first copy of the cluster. The 5880bp preceding the first LORIEN gene copy were compared to the same region of L. major, showing a 93% identity between them. Bioinformatic analysis of this region predicted the presence of a 747-bp ORF encoding a hypothetical protein of 248 amino acids. Transcription of this ORF was confirmed by run-on assays and RT-PCR. Expression of the LORIEN gene was tested in both the promastigote and amastigote stages. Transcription arrest evidenced that LORIEN mRNA stability was very similar in both stages of the parasite life cycle. Protein synthesis inhibition by cycloheximide led to an increase in the steady-state levels of LORIEN transcripts only during the promastigote stage, pointing out to the existence of different stage-dependent mechanisms operating on the post-transcriptional regulation of this gene. The role of the LORIEN untranslated regions (5'UTR and 3'UTR) in post-transcriptional regulation was analysed using the luciferase (luc) reporter gene. Results evidenced that the 5'UTR was responsible for a low reporter gene expression, whereas the intergenic region (IR) between LORIEN and MAT2 genes provided high luc levels. However, the 3'UTR seemed to lack regulatory elements. Basing on these results, a model of regulation for the LORIEN gene is proposed.
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PMID:Characterization of the 5' region of the Leishmania infantum LORIEN/MAT2 gene cluster and role of LORIEN flanking regions in post-transcriptional regulation. 1842 39