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Titolo:
Mitogen-activated protein kinases control p27/Kip1 expression and growth of human melanoma cells
Autore:
Kortylewski, M; Heinrich, PC; Kauffmann, ME; Bohm, M; Mackiewicz, A; Behrmann, I;
Indirizzi:
Rhein Westfal TH Aachen, Dept Biochem, D-52074 Aachen, Germany Rhein Westfal TH Aachen Aachen Germany D-52074 , D-52074 Aachen, Germany Poznan Tech Univ, Dept Canc Immunol, Sch Med Sci, Greatpoland Canc Ctr, PL-61866 Poznan, Poland Poznan Tech Univ Poznan Poland PL-61866 anc Ctr, PL-61866 Poznan, Poland Univ Munster, Dept Dermatol, D-48149 Munster, Germany Univ Munster Munster Germany D-48149 Dermatol, D-48149 Munster, Germany
Titolo Testata:
BIOCHEMICAL JOURNAL
, volume: 357, anno: 2001,
parte:, 1
pagine: 297 - 303
SICI:
0264-6021(20010701)357:<297:MPKCPE>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-MALIGNANT MELANOMA; RAS MUTATIONS; INHIBITOR; P27(KIP1); PROGRESSION; INDUCTION; TRANSFORMATION; INTERLEUKIN-6; PROLIFERATION; ARREST;
Keywords:
PD098059; proliferation; protein stability;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Behrmann, I Rhein Westfal TH Aachen, Dept Biochem, Pauwelsstr 30, D-52074 Aachen, Germany Rhein Westfal TH Aachen Pauwelsstr 30 Aachen Germany D-52074
Citazione:
M. Kortylewski et al., "Mitogen-activated protein kinases control p27/Kip1 expression and growth of human melanoma cells", BIOCHEM J, 357, 2001, pp. 297-303

Abstract

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 upregulation of the cyclin-dependent kinase (Cdk) inhibitor p27/Kip1 and hypophosphorylation of the retinoblastoma protein. Further studies showed that PD098059 treatment significantly decreasedCdk2 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/Kip 1 inhibitor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/04/20 alle ore 22:31:02