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Research article

Involvement of the Ras/extracellular signal-regulated kinase signalling pathway in the regulation of ERCC-1 mRNA levels by insulin

Whaseon LEE-KWON, Deokbae PARK, Michel BERNIER
Biochemical Journal Apr 15, 1998, 331 (2) 591-597; DOI: 10.1042/bj3310591
Whaseon LEE-KWON
Diabetes Section, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, U.S.A.
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Deokbae PARK
Diabetes Section, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, U.S.A.
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Michel BERNIER
Diabetes Section, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, U.S.A.
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  • For correspondence: Bernierm@vax.grc.nia.nih.gov
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Abstract

Expression of DNA repair enzymes, which includes ERCC-1, might be under the control of hormonal and growth factor stimulation. In the present study it was observed that insulin increased ERCC-1 mRNA levels both in Chinese hamster ovary cells overexpressing human insulin receptors (HIRc cells) and in fully differentiated 3T3-L1 adipocytes. To investigate the mechanisms underlying the increase in ERCC-1 gene expression in HIRc cells, we used a variety of pharmacological tools known to inhibit distinct signalling pathways. None of these inhibitors affected the amount of ERCC-1 mRNA in unstimulated cells. The pretreatment of cells with two chemically unrelated phosphatidylinositol 3´-kinase inhibitors, wortmannin and LY294002, failed to block the doubling of ERCC-1 mRNA content by insulin. Similarly, inhibition of pp70 S6 kinase by rapamycin had no apparent effects on this insulin response. In contrast, altering the p21ras-dependent pathway with either manumycin, an inhibitor of Ras farnesylation, or PD98059, an inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (ERK) kinase, suppressed the induction of ERCC-1 mRNA by insulin (P< 0.001). Furthermore inhibition of RNA and protein synthesis negatively regulated the expression of this insulin-regulated gene (P< 0.005). These results suggest that insulin enhances ERCC-1 mRNA levels by the activation of the Ras–ERK-dependent pathway without the involvement of the phosphatidylinositol 3´-kinase/pp70 S6 kinase.

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April 1998

Volume: 331 Issue: 2

Biochemical Journal: 331 (2)
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Involvement of the Ras/extracellular signal-regulated kinase signalling pathway in the regulation of ERCC-1 mRNA levels by insulin
Whaseon LEE-KWON, Deokbae PARK, Michel BERNIER
Biochemical Journal Apr 1998, 331 (2) 591-597; DOI: 10.1042/bj3310591
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Involvement of the Ras/extracellular signal-regulated kinase signalling pathway in the regulation of ERCC-1 mRNA levels by insulin
Whaseon LEE-KWON, Deokbae PARK, Michel BERNIER
Biochemical Journal Apr 1998, 331 (2) 591-597; DOI: 10.1042/bj3310591

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