Reference : Mitogen-activated protein kinases control p27/Kip1 expression and growth of human mel...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Mitogen-activated protein kinases control p27/Kip1 expression and growth of human melanoma cells
Kortylewski, M. [> >]
Heinrich, P. C. [> >]
Kauffmann, M. E. [> >]
Böhm, M. [> >]
MacKiewicz, A. [> >]
Behrmann, Iris mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Biochemical Journal
Portland Press
Pt 1
Yes (verified by ORBilu)
United Kingdom
[en] Tumor Cells, Cultured ; Gene Expression Regulation, Neoplastic ; G1 Phase ; G0 Phase ; Flavonoids ; Enzyme Inhibitors ; Cyclin-Dependent Kinases ; Cyclin-Dependent Kinase 2 ; Cell Division ; Cell Cycle ; Genes, Tumor Suppressor ; Humans ; Retinoblastoma Protein ; Protein-Serine-Threonine Kinases ; Protein Kinases ; Phosphorylation ; Mitogen-Activated Protein Kinases ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinase 1 ; Melanoma ; MAP Kinase Signaling System ; CDC2-CDC28 Kinases
[en] The mitogen-activated protein kinases (MAPKs) extracellular signal-regulated protein kinase (ERK)1 and ERK2, involved in regulating cell growth and differentiation, are constitutively active in A375 and WM239 human melanoma cells. Using PD098059, an inhibitor of MAPK kinase (MEK), we investigated the role of persistently activated ERK1/2 in cell growth. The inhibition of MAPK activity induced a dose-dependent growth arrest in G(0)/G(1) phase. Correspondingly, we observed the up-regulation of the cyclin-dependent kinase (Cdk) inhibitor p27/Kip1 and hypophosphorylation of the retinoblastoma protein. Further studies showed that PD098059 treatment significantly decreased Cdk2 kinase activity, most probably owing to an augmented level of p27/Kip1 associated with cyclin E-Cdk2 complexes. The accumulation of p27/Kip1 protein in A375 cells was attributed to its increased stability. Our findings suggest that constitutively active ERK1/2 kinases contribute to the growth of melanoma cells by negative regulation of the p27/Kip1 inhibitor.

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