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Titolo:
Polyamine depletion stabilizes p53 resulting in inhibition of normal intestinal epithelial cell proliferation
Autore:
Li, L; Rao, JN; Guo, X; Liu, L; Santora, R; Bass, BL; Wang, JY;
Indirizzi:
Baltimore Vet Affairs Med Ctr, Dept Surg, Baltimore, MD 21201 USA Baltimore Vet Affairs Med Ctr Baltimore MD USA 21201 timore, MD 21201 USA Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 , Dept Surg, Baltimore, MD 21201 USA Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 Dept Pathol, Baltimore, MD 21201 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
fascicolo: 3, volume: 281, anno: 2001,
pagine: C941 - C953
SICI:
0363-6143(200109)281:3<C941:PDSPRI>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
GASTROINTESTINAL MUCOSAL GROWTH; AUTOREGULATORY FEEDBACK LOOP; MESSENGER-RNA DEGRADATION; 3' UNTRANSLATED REGION; ORNITHINE DECARBOXYLASE; RICH SEQUENCE; WILD-TYPE; C-MYC; BINDING; EXPRESSION;
Keywords:
ornithine decarboxylase; growth arrest; apoptosis; messenger ribonucleic acid; protein stability; rats;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
59
Recensione:
Indirizzi per estratti:
Indirizzo: Wang, JY Baltimore Vet Affairs Med Ctr, Dept Surg, 10 N Greene St, Baltimore, MD 21201 USA Baltimore Vet Affairs Med Ctr 10 N Greene St Baltimore MD USA 21201
Citazione:
L. Li et al., "Polyamine depletion stabilizes p53 resulting in inhibition of normal intestinal epithelial cell proliferation", AM J P-CELL, 281(3), 2001, pp. C941-C953

Abstract

The p53 nuclear phosphoprotein plays a critical role in transcriptional regulation of target genes involved in growth arrest and apoptosis. The natural polyamines, including spermidine, spermine, and their precursor putrescine, are required for cell proliferation, and decreasing cellular polyaminesinhibits growth of the small intestinal mucosa. In the current study, we investigated the mechanisms of regulation of p53 gene expression by cellularpolyamines and further determined the role of the gene product in the process of growth inhibition after polyamine depletion. Studies were conducted both in vivo and in vitro using rats and the IEC-6 cell line, derived from rat small intestinal crypt cells. Levels for p53 mRNA and protein, transcription and posttranscription of the p53 gene, and cell growth were examined. Depletion of cellular polyamines by treatment with a-difluoromethylornithine (DFMO) increased p53 gene expression and caused growth inhibition in theintact small intestinal mucosa and the cultured cells. Polyamine depletiondramatically increased the stability of p53 mRNA as measured by the mRNA half-life but had no effect on p53 gene transcription in IEC-6 cells. Induction of p53 mRNA levels in DFMO-treated cells was paralleled by an increase in the rate of newly synthesized p53 protein. The stability of p53 protein was also increased after polyamine depletion, which was associated with a decrease in Mdm2 expression. When polyamine-deficient cells were exposed to exogenous spermidine, a decrease in p53 gene expression preceded an increase in cellular DNA synthesis. Inhibition of the p53 gene expression by usingp53 antisense oligodeoxyribonucleotides significantly promoted cell growthin the presence of DFMO. These findings indicate that polyamines downregulate p53 gene expression posttranscriptionally and that growth inhibition ofsmall intestinal mucosa after polyamine depletion is mediated, at least partially, through the activation of p53 gene.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 19:15:49