轻度氧化应激下SENP3延缓p53介导的细胞衰老

SENP3 Postpones Cellular Senescence of P53-mediated Pathway under Mild Oxidative Stress

P53是抑癌基因。P53基因突变或失活都使其丧失抑癌作用。有关p53基因突变的研究较多,但对p53失活尤其是一些具有野生型p53的肿瘤中p53为何未行使其抑癌作用而导致发生肿瘤的仍不清楚。人们推测蛋白质水平上p53的功能性灭活可能是p53表达正常却导致肿瘤形成的原因。本研究发现,轻度氧化应激使表达的SENP3迅速累积,其从核仁移位至核质,抑制了p53的转录活性,从而延缓了依赖p53的细胞衰老。因此,我们认为轻度氧化应激下SENP3的过量表达导致了p53的失活,该研究为进一步阐明p53失活的原因提供了依据。

The p53 tumor suppressor functions as a transcription factor which becomes activated upon a number of diverse stress stimuli including DNA damage, oncogene overexpression or metabolic limitations. Upon activation, p53 triggers growth arrest or apoptosis, which serves to eliminate heavily damaged cells. In 50% of human cancers, the gene encoding p53 is mutated. In the remaining cancers, however, p53 retains its wild-type status but its function is effectively inhibited, little is known the reason. We found that SENP3 protein level was enhanced under mild oxidative stress. Meanwhile, SENP3 dispersed from nucleolus to nuclearplasm. The transcriptional activity of p53 was repressed by overexpression of SENP3. The results showed that overexpression of SENP3 could result in inactivation of p53, and may postpone cell senescence in response to mild oxidative stress. This research will provide a new clew for explaining of p53 inactivation.