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)

Centrosome size varies considerably during the cell cycle; it is greatest during metaphase, partly because of pericentriolar matrix recruitment and an increase in microtubule-organizing activity. However, the mechanism of centrosome maturation during M phase is poorly defined. In the present study, we identified and quantified centrosomal proteins during S and M phases using stable isotope labeling by amino acids in cell culture (SILAC) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). We identified 991 proteins, of which 310 and 325 proteins were upregulated during S and M phases, respectively. Ubiquitinated proteins containing K48- and K63-linked polyubiquitin chains accumulated in the centrosomes during M phase, although 26S proteasome activity in the centrosomes did not markedly differ between S and M phases. Conversely, cytoplasmic dynein, which transports ubiquitinated proteins to the centrosomes, increased 2-fold in the centrosomes during M phase relative to S phase. Furthermore, PYR-41, a ubiquitin E1 inhibitor, reduced centrosome size during metaphase, causing increased aneuploidy. RNA interference suppression of Ecm29, which inhibits proteasome activity, decreased the accumulation of ubiquitinated proteins in the centrosomes. These results show that accumulation of ubiquitinated proteins promotes centrosome maturation during M phase and further suggest a novel function of centrosomes as a scaffold temporarily gathering intracellular ubiquitinated proteins.
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PMID:Centrosomes at M phase act as a scaffold for the accumulation of intracellular ubiquitinated proteins. 2474 17

The accumulations of excess amounts of polyubiquitinated proteins are cytotoxic and frequently observed in pathologic tissue from patients of neurodegenerative diseases. Therefore, optical and non-invasive methods to detect the increase of the amounts of polyubiquitinated proteins in living cells is a promising strategy to find out symptoms and environmental cause of neurodegenerative diseases, also for identifying compounds that could inhibit gathering of polyubiquitinated proteins. Therefore, we generated a pair of fluorescent protein [Azamigreen (Azg) and Kusabiraorange (Kuo)] tagged ubiquitin on its N-terminus (Azg-Ub and Kuo-Ub) and developed an Azg/Kuo-based Fluorescence Resonance Energy Transfer (FRET) assay to estimate the amount of polyubiquitin chains in vitro and in vivo. The FRET intensity was attenuated in the presence of ubiquitin-activating enzyme inhibitor, PYR-41, indicating that both fluorescent ubiquitin is incorporated into ubiquitin chains likewise normal ubiquitin. The FRET intensity was enhanced by the addition of the proteasome inhibitor, MG-132, and was reduced in the presence of the autophagy activator Rapamycin, designating that ubiquitin chains with fluorescent ubiquitin act as the degradation signal equally with normal ubiquitin chains. In summary, the above optical methods provide powerful research tools to estimate the amounts of polyubiquitin chains in vitro and in vivo, especially non-invasively in living cells.
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PMID:An optical and non-invasive method to detect the accumulation of ubiquitin chains. 3113 31