RGD Reference Report - Polyamine depletion induces nucleophosmin modulating stability and transcriptional activity of p53 in intestinal epithelial cells. - Rat Genome Database

RGD Reference Report - Polyamine depletion induces nucleophosmin modulating stability and transcriptional activity of p53 in intestinal epithelial cells. - Rat Genome Database

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General

Polyamine depletion induces nucleophosmin modulating stability and transcriptional activity of p53 in intestinal epithelial cells.
Authors:	Zou, T Rao, JN Liu, L Marasa, BS Keledjian, KM Zhang, AH Xiao, L Bass, BL Wang, JY
Citation:	Zou T, etal., Am J Physiol Cell Physiol. 2005 Sep;289(3):C686-96. Epub 2005 May 4.
RGD ID:	11535017
Pubmed:	PMID:15872011 (View Abstract at PubMed)
DOI:	DOI:10.1152/ajpcell.00085.2005 (Journal Full-text)
Our previous studies have shown that polyamines are required for normal intestinal mucosal growth and that decreased levels of polyamines inhibit intestinal epithelial cell (IEC) proliferation by stabilizing p53 and other growth-inhibiting proteins. Nucleophosmin (NPM) is a multifunctional protein that recently has been shown to regulate p53 activity. In the present study, we sought to determine whether polyamine depletion increases NPM modulating the stability and transcriptional activity of p53 in a normal IEC-6 intestinal epithelial cell line. Depletion of cellular polyamines by alpha-difluoromethylornithine, the specific inhibitor of polyamine biosynthesis, stimulated expression of the NPM gene and induced nuclear translocation of NPM protein. Polyamine depletion stimulated NPM expression primarily by increasing NPM gene transcription and its mRNA stability, and it induced NPM nuclear translocation through activation of phosphorylation of mitogen-activated protein kinase kinase. Increased NPM interacted with p53 and formed a NPM/p53 complex in polyamine-deficient cells. Inhibition of NPM expression by small interfering RNA targeting NPM (siNPM) not only destabilized p53 as indicated by a decrease in its protein half-life but also prevented the increased p53-dependent transactivation as shown by suppression of the p21 promoter activity. Decreased expression of NPM by siNPM also promoted cell growth in polyamine-deficient cells. These results indicate that 1) polyamine depletion increases expression of the NPM gene and enhances NPM nuclear translocation and 2) increased NPM interacts with and stabilizes p53, leading to inhibition of IEC-6 cell proliferation.

Biological Process

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Npm1	Rat	negative regulation of epithelial cell proliferation		IMP			RGD

Molecular Function

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Npm1	Rat	p53 binding		IPI	Tp53 (Rattus norvegicus)		RGD
Tp53	Rat	protein binding		IPI	Npm1 (Rattus norvegicus)		RGD

Genes (Rattus norvegicus)


Npm1 (nucleophosmin 1)	Tp53 (tumor protein p53)