Long Non-coding RNA, PANDA, Contributes to the Stabilization of p53 Tumor Suppressor Protein.
Long Non-coding RNA, PANDA, Contributes to the Stabilization of p53 Tumor Suppressor Protein.
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发表时间：
2016-04
影响因子：
2
通讯作者：
Y. Kotake;K. Kitagawa;T. Ohhata;Satoshi Sakai;C. Uchida;Hiroyuki Niida;Madoka Naemura;M. Kitagawa
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文献类型：
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作者：
Y. Kotake;K. Kitagawa;T. Ohhata;Satoshi Sakai;C. Uchida;Hiroyuki Niida;Madoka Naemura;M. Kitagawa
P21相关非编码RNA DNA损伤激活（PANDA）是DNA损伤诱导的，通过抑制核转录因子Y亚基α（NF-YA）转录因子的功能来抑制细胞凋亡。在此，我们报告PANDA影响p53肿瘤抑制蛋白的调节。材料和方法用PANDA siRNA转染U2 OS细胞。在转染后72小时，对细胞进行免疫印迹和定量逆转录聚合酶链反应。结果PANDA耗竭与p53蛋白水平降低有关，但与p53 mRNA水平无关。p53蛋白的稳定性被PANDA沉默显著降低。蛋白酶体抑制剂MG 132可抑制PANDA沉默引起的p53蛋白降解。此外，PANDA的耗尽防止了p53蛋白的积累，作为DNA损伤的结果，由遗传毒性剂依托泊苷诱导。结论PANDA可稳定p53蛋白在DNA损伤中的表达，为进一步研究p53的调控机制提供了新的思路。
BACKGROUND P21-associated noncoding RNA DNA damage-activated (PANDA) is induced in response to DNA damage and represses apoptosis by inhibiting the function of nuclear transcription factor Y subunit alpha (NF-YA) transcription factor. Herein, we report that PANDA affects regulation of p53 tumor-suppressor protein. MATERIALS AND METHODS U2OS cells were transfected with PANDA siRNAs. At 72 h post-transfection, cells were subjected to immunoblotting and quantitative reverse transcription-polymerase chain reaction. RESULTS Depletion of PANDA was associated with decreased levels of p53 protein, but not p53 mRNA. The stability of p53 protein was markedly reduced by PANDA silencing. Degradation of p53 protein by silencing PANDA was prevented by treatment of MG132, a proteasome inhibitor. Moreover, depletion of PANDA prevented accumulation of p53 protein, as a result of DNA damage, induced by the genotoxic agent etoposide. CONCLUSION These results suggest that PANDA stabilizes p53 protein in response to DNA damage, and provide new insight into the regulatory mechanisms of p53.