Department of Physiological Chemistry I, Biocenter, University of Wuerzburg, Germany.
Oncogene. 2012 Apr 5;31(14):1859-68. doi: 10.1038/onc.2011.364. Epub 2011 Aug 22.
The DREAM complex is an important regulator of mitotic gene expression during the cell cycle. Here we report that inactivation of LIN9, a subunit of DREAM, results in premature senescence, which can be overcome by the SV40 large T (LT) antigen. Together with the observation that p16(INK4a) and p21(Waf1) are upregulated upon loss of LIN9, these results indicate that senescence is triggered by the pRB and p53 tumor suppressor pathways. We also find that LIN9-null cells that escape senescence are chromosomally instable because of compromised mitotic fidelity. SV40 LT-expressing cells that adapt to the loss of LIN9 can grow anchorage-independently in soft agar, a hallmark of oncogenic transformation. Taken together, these results suggest an important role of mitotic gene regulation in the maintenance of genomic stability and tumor suppression.
DREAM 复合物是细胞周期中有丝分裂基因表达的重要调节因子。在这里，我们报告说，DREAM 的一个亚基 LIN9 的失活导致过早衰老，而 SV40 大 T（LT）抗原可以克服这种衰老。与 LIN9 缺失时 p16(INK4a)和 p21(Waf1)上调的观察结果一起，这些结果表明衰老由 pRB 和 p53 肿瘤抑制途径触发。我们还发现，由于有丝分裂保真度受损，逃避衰老的 LIN9 缺失细胞的染色体不稳定。适应 LIN9 缺失的 SV40 LT 表达细胞可以在软琼脂中独立生长，这是致癌转化的一个标志。综上所述，这些结果表明有丝分裂基因调控在维持基因组稳定性和肿瘤抑制方面的重要作用。
