Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/C^(Cdh1)  

作　　者：Fenju Lai Kaishun Hu Yuanzhong Wu Jianjun Tang Yi Sang Jingying Cao Tiebang Kang 

机构地区：[1]State Key Laboratory of Oncology in South China [2]Department of Experimental Research,Sun Yat-sen University Cancer Center,Guangzhou,Guangdong 510060,P.R.China

出　　处：《Chinese Journal of Cancer》2012年第9期440-448,共9页

基　　金：supported by grants from Natural Science Foundation of Guangdong Province(No.10251008901000000 toT.K.);Ph.D.Program Foundation of Ministry of Education of China(No.20100171110079toT.K.);China Post doctoral Science Foundation(No.20110490966)

摘　　要：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.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, Cdhl, 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/Cdh1 that plays a key role during mitotic e xit.

关 键 词：有丝分裂过程 核酸酶 基板 蛋白质含量 人力 DNA链 ICL 泛素化 

分 类 号：S512.4[农业科学—作物学] Q523[生物学—生物化学]