Document Detail

Ubiquitin-dependent pathway is up-regulated in differentiating lens cells.
MedLine Citation:
PMID:  10068483     Owner:  NLM     Status:  MEDLINE    
The mammalian eye lens is composed of two distinct types of cells, epithelial cells and fiber cells. The fiber cells are generated throughout life via continuous differentiation of epithelial cells. Differentiation of lens cells involves dramatic changes in cellular components including altered activity of the ubiquitin dependent pathway. The concentration of high mass ubiquitin conjugates in the mitotically active-, differentiating-equatorial epithelial cells was 5-10 fold higher than that observed in mitotically quiescent, non-differentiated, central epithelial cells, even though there was a significant dilution of non-crystallin proteins due to an increase in level of crystallins in the differentiating cells. Similar observations were made when differentiation was modeled by exposure of lens epithelial explants to bFGF in culture. Activities of ubiquitin-activating enzyme (E1) and ubiquitin-conjugating enzymes (E2s) in the differentiating equatorial epithelial cells were also up to 100% higher than those noted in non-differentiated central epithelial cells and E1 appears to be rate controlling for ubiquitinylation. Consistent with the higher concentrations of high mass ubiquitin conjugates, there was a trend of enhanced ability to execute ATP-dependent protein degradation in the differentiating equatorial epithelial cells as compared with degradation in the non-differentiated central epithelial cells. These data indicate that the ubiquitin dependent pathway is up-regulated during differentiation of lens cells. In the differentiated fibers, the concentration of high mass ubiquitin conjugates and relative activities of E1 and E2s were 50% lower than in the non-differentiated central epithelial cells. In comparison, the concentration of the 110 kDa E1 was unchanged in differentiated fibers. However, if the factor of dilution by the significant increase in the level of crystallins was taken into account, the level or activities of the components of ubiquitin pathway in the differentiated cells was higher than the level noted in non-differentiated cells. These data indicate that, as compared with other non-crystallin proteins, there is differential stabilization and/or synthesis of the 110 kDa E1 and some other components of the ubiquitin dependent pathway in differentiated fibers.
F Shang; X Gong; J W McAvoy; C Chamberlain; T R Nowell; A Taylor
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Experimental eye research     Volume:  68     ISSN:  0014-4835     ISO Abbreviation:  Exp. Eye Res.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-04-27     Completed Date:  1999-04-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370707     Medline TA:  Exp Eye Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  179-92     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Academic Press.
Laboratory for Nutrition and Vision Research, USDA, HNRCA at Tufts University, 711 Washington Street, Boston, MA, 02111, USA.
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MeSH Terms
Cell Differentiation / physiology
Culture Techniques
Electrophoresis, Polyacrylamide Gel
Epithelial Cells / cytology,  metabolism
Lens, Crystalline / cytology*,  metabolism
Ligases / genetics,  metabolism
Peptide Hydrolases / metabolism
RNA, Messenger / genetics
Rats, Inbred F344
Rats, Wistar
Ubiquitin-Activating Enzymes
Ubiquitin-Conjugating Enzymes
Ubiquitin-Protein Ligases
Ubiquitins / metabolism*
Up-Regulation / physiology*
Reg. No./Substance:
0/RNA, Messenger; 0/Ubiquitins; EC 3.4.-/Peptide Hydrolases; EC 6.-/Ligases; EC Enzymes; EC Enzymes; EC Ligases

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