Chan Foong Lyn, Vinod Benjamin, Novy Karel, Schittenhelm Ralf B, Huang Cheng, Udugama Maheshi, Nunez-Iglesias Juan, Lin Jane I, Hii Linda, Chan Julie, Pickett Hilda A, Daly Roger J, Wong Lee H
Department of Biochemistry and Molecular Biology, Cancer Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
Monash Biomedical Proteomics Facility & Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
Nucleic Acids Res. 2017 Dec 1;45(21):12340-12353. doi: 10.1093/nar/gkx904.
AURKB (Aurora Kinase B) is a serine/threonine kinase better known for its role at the mitotic kinetochore during chromosome segregation. Here, we demonstrate that AURKB localizes to the telomeres in mouse embryonic stem cells, where it interacts with the essential telomere protein TERF1. Loss of AURKB function affects TERF1 telomere binding and results in aberrant telomere structure. In vitro kinase experiments successfully identified Serine 404 on TERF1 as a putative AURKB target site. Importantly, in vivo overexpression of S404-TERF1 mutants results in fragile telomere formation. These findings demonstrate that AURKB is an important regulator of telomere structural integrity.
极光激酶B（AURKB）是一种丝氨酸/苏氨酸激酶，因其在染色体分离过程中的有丝分裂动粒作用而广为人知。在此，我们证明AURKB定位于小鼠胚胎干细胞的端粒，在那里它与必需的端粒蛋白TERF1相互作用。AURKB功能丧失会影响TERF1与端粒的结合，并导致端粒结构异常。体外激酶实验成功鉴定出TERF1上的丝氨酸404为推定的AURKB靶位点。重要的是，S404 - TERF1突变体在体内的过表达会导致脆弱端粒的形成。这些发现表明AURKB是端粒结构完整性的重要调节因子。
