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 modification of proteins has traditionally been linked to proteasomal degradation, but it is now well established that it also serves nonproteasomal functions, such as DNA repair, signal transduction and endocytic trafficking among others. It is now emerging that G-protein-coupled receptor (GPCR) downregulation is mediated by receptor ubiquitination. For example, agonist-dependent ubiquitination of the chemokine receptor CXCR4 by the E3 ubiquitin ligase AIP4 (atrophin interacting protein 4) targets CXCR4 for degradation in lysosomes. The ubiquitin moiety on CXCR4 serves as a signal on endosomes for entry into the degradative pathway and long-term attenuation of signaling or downregulation. Several GPCRs have been shown to be ubiquitinated, and ubiquitin-dependent trafficking may represent a general mechanism by which GPCRs are targeted to lysosomes, although some GPCRs that are targeted to lysosomes may not be directly regulated by ubiquitination. Here we describe a simple biochemical assay that we have used to study the ubiquitination of CXCR4 that can be easily applied to study the ubiquitination of any GPCR.
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PMID:Ubiquitination of chemokine receptors. 1944 38

Signal transduction through G-protein-coupled receptors (GPCRs) is central for the regulation of virtually all cellular functions, and it has been widely implicated in human diseases. These receptors activate a common molecular switch that is represented by the heterotrimeric G-protein generating a number of second messengers (cAMP, cGMP, DAG, IP3, Ca2+ etc.), leading to a plethora of diverse cellular responses. Spatiotemporal regulation of signals generated by a given GPCR is crucial for proper signalling and is accomplished by a series of biochemical modifications. Over the past few years, it has become evident that many signalling proteins also undergo ubiquitination, a posttranslational modification that typically leads to protein degradation, but also mediates processes such as protein-protein interaction and protein subcellular localization. The social amoeba Dictyostelium discoideum has proven to be an excellent model to investigate signal transduction triggered by GPCR activation, as cAMP signalling via GPCR is a major regulator of chemotaxis, cell differentiation, and multicellular morphogenesis. Ubiquitin ligases have been recently involved in these processes. In the present review, we will summarize the most significant pathways activated upon GPCRs stimulation and discuss the role played by ubiquitination in Dictyostelium cells.
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PMID:G-Protein Dependent Signal Transduction and Ubiquitination in Dictyostelium. 2904 38