Article

Posttranscriptional regulation of chicken ccn2 gene expression by nucleophosmin/B23 during chondrocyte differentiation.

Biodental Research Center, Okayama University Dental School, Okayama 700-8525, Japan.
Molecular and cellular biology (impact factor: 6.06). 09/2008; 28(19):6134-47. DOI:10.1128/MCB.00495-08 pp.6134-47
Source: PubMed

ABSTRACT CCN2/CTGF is a multifunctional factor that plays a crucial role in the growth and differentiation of chondrocytes. The chicken ccn2 gene is regulated not only at the transcriptional level but also by the interaction between a posttranscriptional element in the 3' untranslated region (3'-UTR) and a cofactor. In the present study, we identified a nucleophosmin (NPM) (also called B23) as this cofactor. Binding of NPM to the element was confirmed, and subsequent analysis revealed a significant correlation between the decrease in cytosolic NPM and the increased stability of the ccn2 mRNA during chondrocyte differentiation in vivo. Furthermore, recombinant chicken NPM enhanced the degradation of chimeric RNAs containing the posttranscriptional cis elements in a chicken embryonic fibroblast extract in vitro. It is noteworthy that the RNA destabilization effect by NPM was far more prominent in the cytosolic extract of chondrocytes than in that of fibroblasts, representing a chondrocyte-specific action of NPM. Stimulation by growth factors to promote differentiation changed the subcellular distribution of NPM in chondrocytes, which followed the expected patterns from the resultant change in the ccn2 mRNA stability. Therefore, the present study reveals a novel aspect of NPM as a key player in the posttranscriptional regulation of ccn2 mRNA during the differentiation of chondrocytes.

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Keywords

3' untranslated region
 
ccn2 mRNA
 
ccn2 mRNA stability
 
chicken ccn2 gene
 
chicken embryonic fibroblast
 
chondrocyte-specific action
 
crucial role
 
cytosolic NPM
 
expected patterns
 
growth factors
 
key player
 
multifunctional factor
 
novel aspect
 
posttranscriptional cis elements
 
posttranscriptional element
 
recombinant chicken NPM
 
resultant change
 
significant correlation
 
subsequent analysis
 
transcriptional level