论文部分内容阅读
Nucleus accumbens-1 (NACl), a nuclear factor of the BTB/POZ gene family, has emerging roles in cancer.We report here that NAC1 acts as a suppressor of cellular senescence in transformed and non-transformed cells, and suppression of senescence by NAC1 serves as an important mechanism contributing to its oncogenic potential.NAC1 deficiency markedly increases senescence and inhibits proliferation in tumor cells treated with sub-lethal doses ofγ-irradiation.In mouse embryonic fibroblasts (MEFs) from NAC1 knockout mice, following infection with a Ras virus, NAC1-/-cells undergo significantly more senescence and are either non-or less transformed in vitro and less tumorigenic in vivo when compared with NACl+/+ cells.We also show that the NACl-caused senescence bypass is mediated by ANp63, which exerts its effect on senescence through p21, and that NACl activates transcription of ANp63.Our results not only reveal a previously unrecognized function of NAC 1, the molecular pathway involved and its impact on pathogenesis of tumor, but also identify a novel senescence suppressor that may be exploited as a potential target for cancer prevention and treatment.