RUVBL2 is a novel repressor of ARF transcription
RUVBL2 is a novel repressor of ARF transcription
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DOI：
10.1016/j.febslet.2012.01.026
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发表时间：
2012-02
期刊：
影响因子：
3.5
通讯作者：
Chongwei Xie;Wenyu Wang;Fan Yang;Mian Wu;Yide Mei
中科院分区：
文献类型：
--
作者：
Chongwei Xie;Wenyu Wang;Fan Yang;Mian Wu;Yide Mei
ARF是仅次于P53的第二种最常见的失活肿瘤抑制因子。它与控制细胞增殖、细胞衰老和肿瘤抑制有关。然而，ARF转录调控的详细机制在很大程度上仍不清楚。在这里，我们报告了RUVBL2作为ARF的一个新的转录抑制因子。RUVBL2的异位表达降低了ARF的水平，而RUVBL2的敲除导致ARF的水平显著升高。此外，RUVBL2以ARF依赖的方式下调P53的水平。在机制上，RUVBL2与ARF启动子的远端区域结合，从而抑制ARF的转录。这些结果提示RUVBL2在ARF-P53途径的调控中起重要作用。
ARF is the second most commonly inactivated tumor suppressor behind p53. It has been implicated in the control of cell proliferation, cell senescence, and tumor suppression. However, the detailed mechanism underlying the transcriptional control of ARF remains largely unknown. Here we report RUVBL2 as a novel transcriptional repressor of ARF. Ectopic expression of RUVBL2 decreases the levels of ARF, whereas knockdown of RUVBL2 results in a marked increase in ARF levels. In addition, RUVBL2 down-regulates the levels of p53 in an ARF-dependent manner. Mechanistically, RUVBL2 binds to the distal region of ARF promoter, thus leading to the repression of ARF transcription. These results suggest an important role of RUVBL2 in the regulation of ARF-p53 pathway.