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Titolo:
Mutational status of the p53 gene modulates the basal level of jun N-terminal kinase and its inducibility by ultraviolet irradiation in A1-5 rat fibroblasts
Autore:
Ramaswamy, NT; Pelling, JC;
Indirizzi:
Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA Univ Kansas Kansas City KS USA 66160 & Lab Med, Kansas City, KS 66160 USA Univ Kansas, Med Ctr, Dept Biochem & Mol Biol, Kansas City, KS 66160 USA Univ Kansas Kansas City KS USA 66160 Mol Biol, Kansas City, KS 66160 USA
Titolo Testata:
MOLECULAR CARCINOGENESIS
fascicolo: 4, volume: 25, anno: 1999,
pagine: 262 - 272
SICI:
0899-1987(199908)25:4<262:MSOTPG>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
MOUSE EPIDERMAL-CELLS; SIGNAL-TRANSDUCTION; PROTEIN-KINASE; HA-RAS; UV-B; ACTIVATION; KERATINOCYTES; STRESS; JNK1; EXPRESSION;
Keywords:
ultraviolet B; ultraviolet C; c jun N-terminal kinase 1; p53;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Pelling, JC Univ Kansas, Med Ctr, Dept Pathol & Lab Med, 3901 Rainbow Blvd, Kansas City, KS 66160 USA Univ Kansas 3901 Rainbow Blvd Kansas City KS USA 66160 160 USA
Citazione:
N.T. Ramaswamy e J.C. Pelling, "Mutational status of the p53 gene modulates the basal level of jun N-terminal kinase and its inducibility by ultraviolet irradiation in A1-5 rat fibroblasts", MOL CARCINO, 25(4), 1999, pp. 262-272

Abstract

Exposure of mammalian cells to ultraviolet (UV) light and other DNA-damaging agents triggers the UV response which is characterized by induction of alarge number of genes including c-fos, c-jun, and the genes For DNA repairenzymes and cell-cycle regulatory proteins such as p21(WAF1) and p53. UponDNA damage, the p53 tumor suppressor protein transmits signals to restrictcell-cycle progression, thereby allowing time For DNA repair to occur. Cells also respond to genotoxic stress by activation of the jun N-terminal kinase (JNK)/stress-activated protein kinase pathway. In this report we investigated the effects of modulation of the level of wild-type and mutant p53 protein on basal and UV-inducible JNK activity We used the A1-5 rat fibroblast cell line, which contains a p53 gene coding for a temperature-sensitive p53 protein, which allows vs to regulate the relative level of wild-type and mutant p53 protein produced in a cell. We measured the relative levels ofJNK activity in sham-irradiated and UV-irradiated cells by using the immune complex kinase assay and then computed the fold induction of JNK after UVexposure. We demonstrated that cells expressing p53 protein in the wild-type conformation (when grown at 32 degrees C) exhibited a very low level of JNK activity that was induced 14- to 16-fold by UVC irradiation. When cellswere grown at 37 degrees C or 39 degrees C to express predominantly mutantp53 protein, basal JNK activity was significantly higher than at 32 degrees C. UVC irradiation of cells expressing mutant p53 protein resulted in JNKactivation, although the overall fold-induction was only two-fold because JNK1 activity was already high in the sham-treated controls. UVB irradiation also induced JNK1 activity, although we again observed a relatively high level of basal JNK activity in sham irradiated cells expressing mutant p53 protein compared with cells expressing wild-type p53. Control experiments confirmed that JNK1 basal activity was not affected by temperature alone. Western blot analysis of cell extracts indicated that expression of p21(WAF) protein was significantly higher in cells expressing wild-type p53 protein and was associated with low basal levels of JNK1 activity. In contrast, cells expressing mutant p53 protein and very low levels of p21(WAF1) protein were found to have a higher level of basal JNK1 activity. We also observed areduced ability to induce JNK1 after UV irradiation of several other cell lines with p53-mutant or p53-null genotypes. Our results provide evidence for a novel connection between p53 status and the basal level of JNK1, a critical enzyme in the stress-activated protein kinase family. In addition, these studies suggest that the presence of mutant p53 protein in a cell not only affects basal activity of JNK1 but also affects the ability of a cell to respond to UV-induced stress by transmitting signals via induction or activation of the JNK1 cascade. (C) 1999 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 03:22:40