Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/CCdh1
Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/CCdh1
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DOI：
10.5732/cjc.012.10144
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发表时间：
2012-09-01
影响因子：
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通讯作者：
Kang, Tiebang
中科院分区：
文献类型：
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作者：
Lai, Fenju;Hu, Kaishun;Kang, Tiebang
FAN1(FANCD2相关核酸酶1，以前被称为KIAA1018)是一种新的核酸酶，与单素化的FANCD2相关，是细胞抵抗DNA链间交联剂(ICL)所必需的。FAN1的调控机制尚不清楚。在这里，我们提供了FAN1在有丝分裂退出过程中降解的证据，表明FAN1可能是后期促进环体复合体(APC/C)的有丝分裂底物。事实上，CDH1，而不是CDC20，能够通过Ken盒和D-box调节FAN1的蛋白水平。此外，FAN1的上调和下调影响了向有丝分裂退出的进程。综上所述，这些数据表明FAN1可能是APC/C-CDH1的一个新的有丝分裂底物，在有丝分裂退出过程中发挥关键作用。
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/C-Cdh1 that plays a key role during mitotic exit.