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Mitogen-Independent Phosphorylation of S6K1 and Decreased Ribosomal S6 Phosphorylation in Senescent Human Fibroblasts
Journal article   Peer reviewed

Mitogen-Independent Phosphorylation of S6K1 and Decreased Ribosomal S6 Phosphorylation in Senescent Human Fibroblasts

Hong Zhang, Henry Hoff, Theresa Marinucci, Vincent J. Cristofalo, Christian Sell and Hua Zhang
Experimental cell research, v 259(1)
25 Aug 2000
DOI: https://doi.org/10.1006/excr.2000.4965
PMID: 10942600
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

p70 S6 kinase phosphorylation protein synthesis ribosome S6K1 senescence
The p70 ribosomal S6 kinase (S6K1) is rapidly activated following growth factor stimulation of quiescent fibroblasts and inhibition of this enzyme results in a G1 arrest. Phosphorylation of the ribosomal S6 protein by S6K1 regulates the translation of both ribosomal proteins and initiation factors, leading to an increase in protein synthesis. We have examined the activation of S6K1 in human fibroblasts following mitogen stimulation. In early passage fibroblasts S6K1 is activated following serum stimulation as evidenced by increased kinase activity and site-specific phosphorylation. In contrast, site-specific phosphorylation of S6K1 at Thr421/Ser424 is diminished in senescent fibroblast cultures. A second phosphorylation site within S6K1 (Ser411) is phosphorylated even in the absence of serum stimulation and the enzyme shows increased phosphorylation as judged by decreased electrophoretic mobility. Inhibitor studies indicate that this phosphorylation is dependent upon the mammalian target of rapamycin, PI 3-kinase, and the MAPK pathway. In order to understand the consequences of the altered phosphorylation of the S6K1, we examined the phosphorylation state of the ribosomal S6 protein. In early passage fibroblasts the ribosomal S6 protein is phosphorylated upon serum stimulation while the phosphorylation of the ribosomal S6 protein is drastically reduced in senescent fibroblasts. These results suggest that the intracellular regulators of S6K1 are altered during replicative senescence leading to a deregulation of the enzyme and a loss of ribosomal S6 phosphorylation.

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23 citations in Web of Science
23 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
Oncology
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