Format

Send to

Choose Destination
J Biol Chem. 2014 Feb 7;289(6):3164-75. doi: 10.1074/jbc.M113.524413. Epub 2013 Dec 19.

Rbm24, an RNA-binding protein and a target of p53, regulates p21 expression via mRNA stability.

Author information

1
From the Comparative Oncology Laboratory, University of California, Davis, California 95616.

Abstract

p21, a cyclin-dependent kinase inhibitor, is necessary for proper control of the cell cycle and premature senescence. Thus, p21 expression needs to be tightly controlled. In this study, we found that Rbm24, an RNA-binding protein and a target gene of the p53 protein, can regulate p21 expression via mRNA stability. Specifically, we showed that Rbm24 is induced by DNA damage and Mdm2 inhibitor Nutlin-3. We also found that p53 protein binds to and activates the promoter of the Rbm24 gene. Moreover, we found that overexpression of Rbm24 increases, whereas knockdown of Rbm24 decreases, p21 mRNA and protein expression. In addition, we demonstrated that overexpression of Rbm24 enhances the half-life of p21 transcript. Consistent with this, we provided evidence that Rbm24 binds to the 3'-untranslated region (3'-UTR) of p21 transcript and an AU/U-rich element in the p21 3'-UTR is necessary for Rbm24 to increase p21 expression. Finally, we showed that the RNA recognition motif in Rbm24 is required for binding to p21 transcript and subsequently for inducing p21 expression. Altogether, we uncovered that Rbm24 is a novel player in the p53 pathway, which may be explored to restore proper cell cycle control in p53-deficient tumors via p21.

KEYWORDS:

Cancer Biology; Cell Cycle; RNA-binding Protein; mRNA Decay; p53

PMID:
24356969
PMCID:
PMC3916521
DOI:
10.1074/jbc.M113.524413
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center