Lai Fenju, Hu Kaishun, Wu Yuanzhong, Tang Jianjun, Sang Yi, Cao Jingying, Kang Tiebang
State Key Laboratory of Oncology in South China, Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, PR China.
Chin J Cancer. 2012 Sep;31(9):440-8. doi: 10.5732/cjc.012.10144. Epub 2012 Aug 2.
A recently identified protein, FAN1 (FANCD2-associated nuclease 1, previously known as KIAA1018), is a novel nuclease associated with monoubiquitinated FANCD2 that is required for cellular resistance against DNA interstrand crosslinking (ICL) agents. The mechanisms of FAN1 regulation have not yet been explored. Here, we provide evidence that FAN1 is degraded during mitotic exit, suggesting that FAN1 may be a mitotic substrate of the anaphase-promoting cyclosome complex (APC/C). Indeed, Cdh1, but not Cdc20, was capable of regulating the protein level of FAN1 through the KEN box and the D-box. Moreover, the up- and down-regulation of FAN1 affected the progression to mitotic exit. Collectively, these data suggest that FAN1 may be a new mitotic substrate of APC/CCdh1 that plays a key role during mitotic exit.
最近发现的一种蛋白质，FAN1（FANCD2相关核酸酶1，以前称为KIAA1018），是一种与单泛素化FANCD2相关的新型核酸酶，它是细胞抵抗DNA链间交联（ICL）剂所必需的。FAN1的调控机制尚未得到探索。在这里，我们提供证据表明FAN1在有丝分裂退出过程中被降解，这表明FAN1可能是后期促进环体复合物（APC/C）的有丝分裂底物。事实上，Cdh1而非Cdc20能够通过KEN盒和D盒调节FAN1的蛋白质水平。此外，FAN1的上调和下调影响了有丝分裂退出的进程。总的来说，这些数据表明FAN1可能是APC/CCdh1的一种新的有丝分裂底物，在有丝分裂退出过程中起关键作用。
