| Ubiquitin-conjugating enzyme 3 delays human lens epithelial cells in metaphase. | |
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MedLine Citation:
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PMID: 16565361 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Ubc3/Cdc34 is a ubiquitin-conjugating enzyme (Ubc) with well established functions in the G1-to-S-phase transition. Expecting to find similar effects in human lens epithelial cells (HLECs), the authors explored roles for this ubiquitin-conjugating enzyme in regulation of the HLEC cycle. METHODS: Catalytically incompetent Ubc3 (C88S, L97S), wild-type (wt)Ubc3, and mutant (mt)Ubc2 (C93A) were expressed in HLECs, by using an adenoviral vector, and cell cycle progression was assessed. RESULTS: Expression of mt- and wtUbc3, but not empty virus or mtUbc2, delayed the cell cycle in metaphase, rather than the expected G1 phase. Expression of both Ubc3s also stabilized M-phase regulators, cyclin A, cyclin B, and securin. Thus, it appeared that the Ubc3 enzymes were playing roles different from canonical proteolytic functions in targeting G1/S regulators for degradation. We also directly investigated the effect of inhibiting the proteasome on the cell cycle of HLECs. When the proteasome inhibitor was added to S-phase cells, the M-phase regulators were stabilized, and the cells were arrested in the G2/M phase. In contrast, if the proteasome inhibitor was added before the cells entered the S phase, stabilization of the G1 kinase inhibitors p21WAF and p27KIP was observed and the cells were arrested in the G1 phase. CONCLUSIONS: The ubiquitin-proteasome pathway is involved in regulation of transitions between all phases of the HLEC cycle. However, in contrast with previously described roles for Ubc3 in governing G1/S transitions, expression of Ubc3 delays the HLEC cycle in metaphase. The data suggest novel roles for Ubc3 that do not involve the transfer of ubiquitin in the M phase in the HLEC cell cycle. |
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Authors:
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Qing Liu; Fu Shang; Elizabeth Whitcomb; Weimin Guo; Wei Li; Allen Taylor |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Investigative ophthalmology & visual science Volume: 47 ISSN: 0146-0404 ISO Abbreviation: Invest. Ophthalmol. Vis. Sci. Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-03-27 Completed Date: 2006-04-27 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7703701 Medline TA: Invest Ophthalmol Vis Sci Country: United States |
Other Details:
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Languages: eng Pagination: 1302-9 Citation Subset: IM |
Affiliation:
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Laboratory for Nutrition and Vision Research, JMUSDA-HNRCA at Tufts University, Boston, Massachusetts 02111, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenoviridae
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genetics Blotting, Western Cell Culture Techniques Cyclin-Dependent Kinase Inhibitor p21 / metabolism Cyclin-Dependent Kinase Inhibitor p27 / metabolism Epithelial Cells / cytology Flow Cytometry Gene Expression Regulation, Enzymologic / physiology Genetic Vectors Humans Lens, Crystalline / cytology* Metaphase / physiology* Microscopy, Fluorescence Microtubules / metabolism Nocodazole / pharmacology Ubiquitin-Protein Ligase Complexes / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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EY11717/EY/NEI NIH HHS; EY13078/EY/NEI NIH HHS; EY13250/EY/NEI NIH HHS; EY14083-01A2/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cdkn1a protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p21; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 31430-18-9/Nocodazole; EC 6.3.2.19/Ubiquitin-Protein Ligase Complexes; EC 6.3.2.19/anaphase-promoting complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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