p53 transactivation is involved in the antiproliferative activity of the putative tumor suppressor RBM5
p53 transactivation is involved in the antiproliferative activity of the putative tumor suppressor RBM5
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DOI：
10.1002/ijc.25345
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发表时间：
2011-01-15
影响因子：
6.4
通讯作者：
Brachmann, Rainer K.
中科院分区：
文献类型：
--
作者：
Kobayashi, Takahiko;Ishida, Junich;Brachmann, Rainer K.
RBM5(RNA结合基序蛋白5)是一种含有两个RNA识别基序的核RNA结合蛋白。RBM5基因位于肿瘤抑制基因3p21.3。该基因缺失是肺癌中最常见的基因改变，但也在其他人类癌症中发现。已知RBM5可诱导细胞凋亡和细胞周期停滞，但RBM5功能的分子机制尚不清楚。在这里，我们表明RBM5对于肿瘤抑制蛋白P53的活性是重要的。过表达RBM5可增强P53对细胞生长和集落形成的抑制作用。在报告基因检测中，RBM5的表达增强了P53的转录活性，并导致内源性P53靶基因的mRNA和蛋白水平增加。相反，shRNA介导的内源性RBM5基因敲除导致P53转录活性降低，内源性P53靶基因的mRNA和蛋白水平降低。DNA损伤后，RBM5影响内源性P53的蛋白水平，但不影响其mRNA水平，提示RBM5通过转录后机制促进P53的活性。我们的结果表明，RBM5参与了DNA损伤后P53的转录活性，并且由RBM5介导的生长抑制和凋亡与肿瘤抑制蛋白P53的活性有关。
RBM5 (RNA-binding motif protein 5) is a nuclear RNA binding protein containing 2 RNA recognition motifs. The RBM5 gene is located at the tumor suppressor locus 3p21.3. Deletion of this locus is the most frequent genetic alteration in lung cancer, but is also found in other human cancers. RBM5 is known to induce apoptosis and cell cycle arrest but the molecular mechanisms of RBM5 function are poorly understood. Here, we show that RBM5 is important for the activity of the tumor suppressor protein p53. Overexpression of RBM5 enhanced p53-mediated inhibition of cell growth and colony formation. Expression of RBM5 augmented p53 transcriptional activity in reporter gene assays and resulted in increased mRNA and protein levels for endogenous p53 target genes. In contrast, shRNA-mediated knockdown of endogenous RBM5 led to decreased p53 transcriptional activity and reduced levels of mRNA and protein for endogenous p53 target genes. RBM5 affected protein, but not mRNA, levels of endogenous p53 after DNA damage suggest that RBM5 contributes to p53 activity through post-transcriptional mechanisms. Our results show that RBM5 contributes to p53 transcriptional activity after DNA damage and that growth suppression and apoptosis mediated by RBM5 are linked to activity of the tumor suppressor protein p53.