RecQL4-Aurora B kinase axis is essential for cellular proliferation, cell cycle progression, and mitotic integrity.
RecQL4-Aurora B kinase axis is essential for cellular proliferation, cell cycle progression, and mitotic integrity.
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RecQL4-Aurora B 激酶轴对于细胞增殖、细胞周期进展和有丝分裂完整性至关重要。
DOI：
10.1038/s41389-018-0080-4
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发表时间：
2018-09-12
期刊：
影响因子：
6.2
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Fang H;Niu K;Mo D;Zhu Y;Tan Q;Wei D;Li Y;Chen Z;Yang S;Balajee AS;Zhao Y
人类RecQL4解旋酶在维持基因组稳定性中起着至关重要的作用。RecQL4解旋酶突变导致三种临床相关的常染色体隐性遗传病：rothmond - thomson综合征（RTS）、RAPADILINO和Baller-Gerold综合征。除了几个早衰特征外，RTS患者的特征是非整倍体，包括单个染色体的丢失或获得。据报道，在缺乏RecQL4的RTS患者中存在染色体镶嵌现象和涉及第2、7和8号染色体的同工染色体，但RecQL4在染色体分离/稳定性中的确切作用仍有待阐明。在这里，我们证明了RecQL4在物理和功能上与Aurora B激酶（AURKB）相互作用，并通过抑制其泛素化过程来稳定其表达。我们的研究表明，RecQL4的n端与AURKB的催化结构域相互作用。引人注目的是，抑制RecQL4可降低AURKB的表达，导致有丝分裂不规则和凋亡细胞死亡。抑制RecQL4增加了G2/M期细胞的比例，随后是广泛的细胞死亡，可能是由于有丝分裂不规则性的积累。这两种缺陷（细胞在G2/M期的积累和不适当的有丝分裂进入亚g1期）都与AURKB的异位表达相辅相成。最后，提供了人类端粒酶逆转录酶和RecQL4对RTS成纤维细胞稳定永生化和长寿的要求的证据。总之，我们的研究表明，RecQL4-AURKB轴对人类细胞的细胞增殖、细胞周期进展和有丝分裂稳定性至关重要。
Human RecQL4 helicase plays critical roles in the maintenance of genomic stability. Mutations in RecQL4 helicase results in three clinically related autosomal recessive disorders: Rothmund–Thomson syndrome (RTS), RAPADILINO, and Baller–Gerold syndrome. In addition to several premature aging features, RTS patients are characterized by aneuploidy involving either loss or gain of a single chromosome. Chromosome mosaicism and isochromosomes involving chromosomes 2, 7, and 8 have been reported in RecQL4-deficient RTS patients, but the precise role of RecQL4 in chromosome segregation/stability remains to be elucidated. Here, we demonstrate that RecQL4 physically and functionally interacts with Aurora B kinase (AURKB) and stabilizes its expression by inhibiting its ubiquitination process. Our study indicates that the N-terminus of RecQL4 interacts with the catalytic domain of AURKB. Strikingly, RecQL4 suppression reduces the expression of AURKB leading to mitotic irregularities and apoptotic cell death. RecQL4 suppression increases the proportion of cells at the G2/M phase followed by an extensive cell death, presumably owing to the accumulation of mitotic irregularities. Both these defects (accumulation of cells at G2/M phase and an improper mitotic exit to sub-G1) are complemented by the ectopic expression of AURKB. Finally, evidence is provided for the requirement of both human telomerase reverse transcriptase and RecQL4 for stable immortalization and longevity of RTS fibroblasts. Collectively, our study suggests that the RecQL4–AURKB axis is essential for cellular proliferation, cell cycle progression, and mitotic stability in human cells.
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影响因子：
16.6
作者：
Bekier, Michael E.;Mazur, Travis;Rashid, Maisha S.;Taylor, William R.
通讯作者：
Taylor, William R.
DOI：
10.1083/jcb.200906117
发表时间：
2009-12-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Maerki S;Olma MH;Staubli T;Steigemann P;Gerlich DW;Quadroni M;Sumara I;Peter M
通讯作者：
Peter M
影响因子：
16.6
作者：
Croteau DL;Popuri V;Opresko PL;Bohr VA
通讯作者：
Bohr VA
DOI：
10.4196/kjpp.2015.19.2.119
发表时间：
2015-03
期刊：
The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology
影响因子：
--
作者：
Jin H;Yoon HE;Lee JS;Kim JK;Myung SH;Lee YS
通讯作者：
Lee YS
影响因子：
11.5
作者：
Mita, Alain C.;Mita, Monica M.;Giles, Francis J.
通讯作者：
Giles, Francis J.