Up-regulation of nucleolin mRNA and protein in peripheral blood mononuclear cells by extracellular-regulated kinase

Cara J. Westmark, James S. Malter

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The signal transduction pathways regulating nucleolin mRNA and protein production have yet to be elucidated. Peripheral blood mononuclear cells treated with phorbol 12-myristate 13-acetate showed steady state levels of nucleolin mRNA that were 2-2.5-fold greater than untreated control cells. The up-regulation of nucleolin mRNA was substantially repressed by U0126, a specific inhibitor that blocks phosphorylation of extracellular-regulated kinase (ERK). Calcium ionophores A23167 and ionomycin also activated ERK and substantially elevated nucleolin mRNA levels, demonstrating phorbol 12-myristate 13-acetate and calcium signaling converge on ERE. Drugs that affected protein kinase C, protein kinase A, and phospholipase C signal transduction pathways did not alter nucleolin mRNA levels significantly. The half-life of nucleolin mRNA increased from 1.8 h in resting cells to 3.2 h with phorbol ester activation, suggesting ERK-mediated posttranscriptional regulation. Concomitantly, full-length nucleolin protein was increased. The higher levels of nucleolin protein were accompanied by increased binding of a 70-kDa nucleolin fragment to the 29-base instability element in the 3′-untranslated region of amyloid precursor protein (APP) mRNA in gel mobility shift assays. Supplementation of rabbit reticulocyte lysate with nucleolin decreased APP mRNA stability and protein production. These data suggest ERK up-regulates nucleolin posttranscriptionally thereby controlling APP production.

Original languageEnglish (US)
Pages (from-to)1119-1126
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number2
DOIs
StatePublished - Jan 12 2001

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Blood Cells
Blood
Phosphotransferases
Up-Regulation
Messenger RNA
Proteins
Amyloid beta-Protein Precursor
Signal transduction
calcium acetate
Signal Transduction
Acetates
nucleolin
Phosphorylation
Ionomycin
Calcium Signaling
Calcium Ionophores
Protein Stability
Reticulocytes
RNA Stability
3' Untranslated Regions

ASJC Scopus subject areas

  • Biochemistry

Cite this

Up-regulation of nucleolin mRNA and protein in peripheral blood mononuclear cells by extracellular-regulated kinase. / Westmark, Cara J.; Malter, James S.

In: Journal of Biological Chemistry, Vol. 276, No. 2, 12.01.2001, p. 1119-1126.

Research output: Contribution to journalArticle

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