Journal article
Role of the Raf/MEK/ERK and the PI3K/Akt(PKB) pathways in fibroblast senescence
Experimental gerontology, v 37(10), pp 1149-1156
2002
PMID: 12470826
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Replicative senescence is characterized by numerous phenotypic alterations including loss of proliferative capacity and numerous changes in gene expression such as impaired serum inducibility of the immediate early gene
c-fos and increased expression of collagenase. Transcription of
c-fos in response to mitogens depends on the activation of a multiprotein complex formed on the
c-fos serum response element (SRE), which includes the transcription factors serum response factor (SRF) and ternary complex factor (TCF). TCF is activated after phosphorylation by the Extracellular signals Regulated Kinase 1 and 2 (ERK1/2), two kinases of the Raf/MEK/ERK signaling pathway. We have previously demonstrated that collagenase expression is under positive regulation by the transcription factor FKHRL1 and that this transcription factor is under negative regulation by the phosphatidylinositol 3-kinase(PI3K)/Akt(PKB) pathway. Although total activity of ERK and Akt was similar in total cell lysates from early and late passage fibroblasts our data indicate that in senescent cells neither ERK nor Akt are able to phosphorylate efficiently their nuclear targets. Our findings suggest that although they can be fully activated in the cytosol of both early and late passage cells, the Raf/MEK/ERK and the PI3K/Akt pathways, which are essential for cellular proliferation, are down regulated in the nuclei of senescent cells.
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Details
- Title
- Role of the Raf/MEK/ERK and the PI3K/Akt(PKB) pathways in fibroblast senescence
- Creators
- Antonello Lorenzini - Lankenau Institute for Medical ResearchMaria Tresini - Lankenau Institute for Medical ResearchMadhu Mawal-Dewan - Lankenau Institute for Medical ResearchLorenza Frisoni - Lankenau Institute for Medical ResearchHong Zhang - Lankenau Institute for Medical ResearchRobert G. Allen - Lankenau Institute for Medical ResearchChristian Sell - Lankenau Institute for Medical ResearchVincent J. Cristofalo - Thomas Jefferson University
- Publication Details
- Experimental gerontology, v 37(10), pp 1149-1156
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000179722100003
- Scopus ID
- 2-s2.0-0036815365
- Other Identifier
- 991020099677804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Geriatrics & Gerontology