Ubiquitin–Proteasome Pathway Function Is Required for Lens Cell Proliferation and Differentiation

2006 ◽  
Vol 47 (6) ◽  
pp. 2569 ◽  
Author(s):  
Weimin Guo ◽  
Fu Shang ◽  
Qing Liu ◽  
Lyudmila Urim ◽  
Minlei Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Ubiquitin Proteasome Pathway ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Pathway Function ◽  
Ubiquitin Proteasome ◽  
Lens Cell ◽  
Proteasome Pathway

FGF-induced lens cell proliferation and differentiation is dependent on MAPK (ERK1/2) signalling

Development ◽  
2001 ◽  
Vol 128 (24) ◽  
pp. 5075-5084 ◽  
Author(s):  
Frank J. Lovicu ◽  
John W. McAvoy
Keyword(s):  
Cell Proliferation ◽  
Morphological Changes ◽  
Specific Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
Differentiation Markers ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Lens Fibre ◽  
Lens Cell

Members of the fibroblast growth factor (FGF) family induce lens epithelial cells to undergo cell division and differentiate into fibres; a low dose of FGF can stimulate cell proliferation (but not fibre differentiation), whereas higher doses of FGF are required to induce fibre differentiation. To determine if these cellular events are regulated by the same signalling pathways, we examined the role of mitogen-activated protein kinase (MAPK) signalling in FGF-induced lens cell proliferation and differentiation. We show that FGF induced a dose-dependent activation of extracellular regulated kinase 1/2 (ERK1/2) as early as 15 minutes in culture, with a high (differentiating) dose of FGF stimulating a greater level of ERK phosphorylation than a lower (proliferating) dose. Subsequent blocking experiments using UO126 (a specific inhibitor of ERK activation) showed that activation of ERK is required for FGF-induced lens cell proliferation and fibre differentiation. Interestingly, inhibition of ERK signalling can block the morphological changes associated with FGF-induced lens fibre differentiation; however, it cannot block the synthesis of some of the molecular differentiation markers, namely, β-crystallin. These findings are consistent with the in vivo distribution of the phosphorylated (active) forms of ERK1/2 in the lens. Taken together, our data indicate that different levels of ERK signalling may be important for the regulation of lens cell proliferation and early morphological events associated with fibre differentiation; however, multiple signalling pathways are likely to be required for the process of lens fibre differentiation and maturation.

scholarly journals Use of a double-label method to detect rapid changes in the rate of cell proliferation.

1992 ◽  
Vol 40 (5) ◽  
pp. 619-627 ◽  
Author(s):  
G A Hyatt ◽  
D C Beebe
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Short Pulse ◽  
S Phase ◽  
Fiber Cells ◽  
Label Method ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Double Label ◽  
Lens Cell

We developed a double-label method to directly measure the rate at which cells enter S-phase of the cell cycle. All cells in S-phase were first labeled with a short pulse of [3H]-thymidine. This was followed by a longer incubation in bromodeoxyuridine (BrdU), a thymidine analogue. Nuclei labeled with [3H]-thymidine were detected by autoradiography and those labeled with BrdU by immunocytochemistry. Cells labeled only with BrdU must have entered S-phase at some time after the end of the [3H]-thymidine pulse. Thus, the rate of entry of cells into S-phase could be determined. This method was shown to be more accurate and more sensitive than determining changes in the rate at which cells entered S-phase with a continuous labeling protocol. It was possible to detect changes in proliferative activity that occurred in less than 1 hr. We used this double-label technique to study changes in the cell cycle during the terminal differentiation of chicken embryo lens fiber cells. These studies revealed differences in the effects of several treatments known to stimulate fiber cell differentiation. They also demonstrated the presence in the embryonic eye of factors that stimulate and prevent lens cell proliferation and differentiation.

scholarly journals Cyclin G2 Is Degraded through the Ubiquitin-Proteasome Pathway and Mediates the Antiproliferative Effect of Activin Receptor-like Kinase 7

2008 ◽  
Vol 19 (11) ◽  
pp. 4968-4979 ◽  
Author(s):  
Guoxiong Xu ◽  
Stefanie Bernaudo ◽  
Guodong Fu ◽  
Daniel Y. Lee ◽  
Burton B. Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Antiproliferative Effect ◽  
Ovarian Cancer Cells ◽  
Ubiquitin Proteasome Pathway ◽  
Receptor Like Kinase ◽  
Cyclin G2 ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

We have previously reported that Nodal, a member of the TGF-β superfamily, acts through activin receptor-like kinase 7 (ALK7) to inhibit ovarian cancer cell proliferation. To determine the mechanism underlying their effects, a cell cycle gene array was performed and cyclin G2 mRNA was found to be strongly up-regulated by Nodal and ALK7. To study the function and regulation of cyclin G2 in ovarian cancer cells, expression constructs were generated. We found that cyclin G2 protein level decreased rapidly after transfection, and this decrease was prevented by 26S proteasome inhibitors. Immunoprecipitation and pull-down studies showed that ubiquitin, Skp1, and Skp2 formed complexes with cyclin G2. Knockdown of Skp2 by siRNA increased, whereas overexpression of Skp2 decreased cyclin G2 levels. Nodal and ALK7 decreased the expression of Skp1 and Skp2 and increased cyclin G2 levels. Overexpression of cyclin G2 inhibited cell proliferation whereas cyclin G2-siRNA reduced the antiproliferative effect of Nodal and ALK7. Taken together, these findings provide strong evidence that cyclin G2 is degraded by the ubiquitin–proteasome pathway and that Skp2 plays a role in regulating cyclin G2 levels. Furthermore, our results also demonstrate that the antiproliferative effect of Nodal/ALK7 on ovarian cancer cells is in part mediated by cyclin G2.

scholarly journals The Ubiquitin-Proteasome Pathway in Huntington's Disease

2008 ◽  
Vol 8 ◽  
pp. 421-433 ◽  
Author(s):  
Siddhartha Mitra ◽  
Steven Finkbeiner
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Inclusion Bodies ◽  
Mutant Huntingtin ◽  
Polyglutamine Expansion ◽  
Ubiquitin Proteasome Pathway ◽  
Intracellular Protein Degradation ◽  
Pathway Function ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

The accumulation of mutant protein is a common feature of neurodegenerative disease. In Huntington's disease, a polyglutamine expansion in the huntingtin protein triggers neuronal toxicity. Accompanying neuronal death, mutant huntingtin aggregates in large macromolecular structures called inclusion bodies. The function of the machinery for intracellular protein degradation is linked to huntingtin toxicity and components of this machinery colocalize with inclusion bodies. An increasing body of evidence implicates the ubiquitin-proteasome pathway in the failure of cells to degrade mutant huntingtin. A number of potential mechanisms that link compromised ubiquitin-proteasome pathway function and neurodegeneration have been proposed and may offer opportunities for therapeutic intervention.

scholarly journals NRAGE promotes cell proliferation by stabilizing PCNA in a ubiquitin–proteasome pathway in esophageal carcinomas

2014 ◽  
Vol 35 (7) ◽  
pp. 1643-1651 ◽  
Author(s):  
Qingyuan Yang ◽  
Chao Ou ◽  
Mei Liu ◽  
Weifan Xiao ◽  
Chuanjun Wen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Esophageal Carcinomas
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