Xu Enshun, Zhang Jin, Zhang Min, Jiang Yuqian, Cho Seong-Jun, Chen Xinbin
Comparative Oncology Laboratory, University of California at Davis, Davis, CA 95616.
Mol Cancer Res. 2014 Mar;12(3):359-69. doi: 10.1158/1541-7786.MCR-13-0526. Epub 2013 Dec 27.
p63, a p53 family member, plays pivotal roles in epidermal development, aging, and tumorigenesis. Thus, understanding how p63 expression is controlled has biological and clinical importance. RBM24 is an RNA-binding protein and shares a high sequence similarity with RBM38, a critical regulator of p63. In this study, we investigated whether RBM24 is capable of regulating p63 expression. Indeed, we found that ectopic expression of RBM24 decreased, whereas knockdown of RBM24 increased, the levels of p63 transcript and protein. To explore the underlying mechanism, we found that RBM24 was able to bind to multiple regions in the p63 3' untranslated region and, subsequently, destabilize p63 transcript. Furthermore, we showed that the 3' untranslated region in p63 transcript and the RNA-binding domain in RBM24 were required for RBM24 to bind p63 transcript and consequently, inhibit p63 expression. Taken together, our data provide evidence that RBM24 is a novel regulator of p63 via mRNA stability.
Our study suggests that p63 is regulated by RBM24 via mRNA stability, which gives an insight into understanding how posttranscriptional regulatory mechanisms contribute to p63 expression.
p63是一种p53家族成员，在表皮发育、衰老和肿瘤发生中起关键作用。因此，了解p63的表达是如何被调控的具有生物学和临床重要性。RBM24是一种RNA结合蛋白，与p63的关键调节因子RBM38具有高度的序列相似性。在本研究中，我们调查了RBM24是否能够调节p63的表达。事实上，我们发现RBM24的异位表达降低了p63转录本和蛋白的水平，而敲低RBM24则增加了它们的水平。为了探究潜在机制，我们发现RBM24能够结合p63 3'非翻译区的多个区域，随后使p63转录本不稳定。此外，我们表明p63转录本中的3'非翻译区和RBM24中的RNA结合结构域是RBM24结合p63转录本并因此抑制p63表达所必需的。综上所述，我们的数据提供了证据表明RBM24是通过mRNA稳定性对p63进行调控的新调节因子。
我们的研究表明p63通过mRNA稳定性受RBM24调控，这为理解转录后调控机制如何影响p63表达提供了思路。
