German Cancer Research Center (dkfz), DKFZ-ZMBH Alliance, Cellular Senescence Group, Heidelberg, Germany.
Bioessays. 2013 Jan;35(1):55-64. doi: 10.1002/bies.201200060. Epub 2012 Nov 21.
In response to DNA-damage, cells have to decide between different cell fate programmes. Activation of the tumour suppressor HIPK2 specifies the DNA damage response (DDR) and tips the cell fate balance towards an apoptotic response. HIPK2 is activated by the checkpoint kinase ATM, and triggers apoptosis through regulatory phosphorylation of a set of cellular key molecules including the tumour suppressor p53 and the anti-apoptotic corepressor CtBP. Recent work has identified HIPK2 as a regulator of the ultimate step in cytokinesis: the abscission of the mother and daughter cells. Since proper cytokinesis is essential for genome stability and maintenance of correct ploidy, this finding sheds new light on the tumour suppressor function of HIPK2. Here we highlight the molecular mechanisms coordinating HIPK2 function and discuss its emerging role as a tumour suppressor.
细胞在应对 DNA 损伤时，必须在不同的细胞命运程序之间做出选择。肿瘤抑制因子 HIPK2 的激活决定了 DNA 损伤反应（DDR），并使细胞命运平衡向凋亡反应倾斜。HIPK2 被检查点激酶 ATM 激活，并通过调节磷酸化一组包括肿瘤抑制因子 p53 和抗凋亡核心抑制因子 CtBP 在内的细胞关键分子来触发细胞凋亡。最近的研究将 HIPK2 鉴定为细胞分裂后期的最后一步的调节剂：母细胞和子细胞的分离。由于适当的细胞分裂对于基因组稳定性和维持正确的倍性至关重要，这一发现为 HIPK2 的肿瘤抑制功能提供了新的视角。本文强调了协调 HIPK2 功能的分子机制，并讨论了其作为肿瘤抑制因子的新兴作用。
