Journal article
Metabolic stabilization of MAP kinase phosphatase-2 in senescence of human fibroblasts
Experimental cell research, v 290(2)
01 Nov 2003
PMID: 14567979
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cellular senescence is characterized by impaired cell proliferation. We have previously shown that, relative to the young counterpart, senescent WI-38 human fibroblasts display a decreased abundance of active phosphorylated ERK (p-ERK) in the nucleus. We have tested the hypothesis that this is due to elevated levels of nuclear MAP kinase phosphatase (MKP) activity in senescent cells. Our results indicate that the activity and abundance of MKP-2 is increased in senescent fibroblasts, compared to their young counterparts. Further analysis indicates that it is MKP-2 protein, but not MKP-2 mRNA level, that is increased in senescent cells. This increase is the result of the increased stability of MKP-2 protein against proteolytic degradation. The degradation of MKPs was impaired by proteasome inhibitors both in young and old WI-38 cells, indicating that proteasome activity is involved in the degradation of MKPs. Finally, our results indicate that proteasome activity, in general, is diminished in senescent fibroblasts. Taken together, these data indicate that the increased level and activity of MKP-2 in senescent WI-38 cells are the consequence of impaired proteosomal degradation, and this increase is likely to play a significant role in the decreased levels of p-ERK in the nucleus of senescent cells.
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Details
- Title
- Metabolic stabilization of MAP kinase phosphatase-2 in senescence of human fibroblasts
- Creators
- Claudio Torres - Lankenau Institute for Medical ResearchMary Kay Francis - Lankenau Institute for Medical ResearchAntonello Lorenzini - Lankenau Institute for Medical ResearchMaria Tresini - Lankenau Institute for Medical ResearchVincent J Cristofalo - Lankenau Institute for Medical Research
- Publication Details
- Experimental cell research, v 290(2)
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000186132500002
- Scopus ID
- 2-s2.0-0142011160
- Other Identifier
- 991020836220004721
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- Web of Science research areas
- Cell Biology
- Oncology