TY - JOUR
T1 - Rbm24, a target of p53, is necessary for proper expression of p53 and heart development
AU - Zhang, Min
AU - Zhang, Yanhong
AU - Xu, Enshun
AU - Mohibi, Shakur
AU - de Anda, Danielle Michelle
AU - Jiang, Yuqian
AU - Zhang, Jin
AU - Chen, Xinbin
PY - 2018/1/22
Y1 - 2018/1/22
N2 - Activation of p53-dependent apoptosis is critical for tumor suppression but aberrant activation of p53 also leads to developmental defects and heart failure. Here, we found that Rbm24 RNA-binding protein, a target of p53, regulates p53 mRNA translation. Mechanistically, we found that through binding to p53 mRNA and interaction with translation initiation factor eIF4E, Rbm24 prevents eIF4E from binding to p53 mRNA and inhibits the assembly of translation initiation complex. Importantly, we showed that mice deficient in Rbm24 die in utero due to the endocardial cushion defect in the heart at least in part due to aberrant activation of p53-dependent apoptosis. We also showed that the heart developmental defect in Rbm24-null mice can be partially rescued by p53 deficiency through decreased apoptosis in the heart. Together, we postulate that the p53-Rbm24 loop is critical for the heart development and may be explored for mitigating congenital heart diseases and heart failure.
AB - Activation of p53-dependent apoptosis is critical for tumor suppression but aberrant activation of p53 also leads to developmental defects and heart failure. Here, we found that Rbm24 RNA-binding protein, a target of p53, regulates p53 mRNA translation. Mechanistically, we found that through binding to p53 mRNA and interaction with translation initiation factor eIF4E, Rbm24 prevents eIF4E from binding to p53 mRNA and inhibits the assembly of translation initiation complex. Importantly, we showed that mice deficient in Rbm24 die in utero due to the endocardial cushion defect in the heart at least in part due to aberrant activation of p53-dependent apoptosis. We also showed that the heart developmental defect in Rbm24-null mice can be partially rescued by p53 deficiency through decreased apoptosis in the heart. Together, we postulate that the p53-Rbm24 loop is critical for the heart development and may be explored for mitigating congenital heart diseases and heart failure.
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U2 - 10.1038/s41418-017-0029-8
DO - 10.1038/s41418-017-0029-8
M3 - Article
C2 - 29358667
AN - SCOPUS:85040778300
SP - 1
EP - 13
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
SN - 1350-9047
ER -