A bromodomain protein, MCAP, associates with mitotic chromosomes and effects, G2-to-M transition

A bromodomain protein, MCAP, associates with mitotic chromosomes and effects, G2-to-M transition
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DOI:
10.1128/mcb.20.17.6537-6549.2000
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发表时间:
2000-09-01
影响因子:
5.3
通讯作者:
Ozato, K
Ozato, K
中科院分区:
生物学2区
文献类型:
--
作者:
Dey, A;Ellenberg, J;Ozato, K

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我们描述了一种称为有丝分裂染色体相关蛋白(MCAP)的新型核因子,它属于溴结构域超家族中鲜为人知的BET亚群。200 kda MCAP的表达与细胞分裂有关,因为它是由生长刺激诱导和生长抑制抑制。MCAP最显著的特征是它在有丝分裂期间与染色体的关联,这是在大多数核调节因子被释放到细胞质中时观察到的,与转录的全局停止相一致。MCAP主要与常染色质相互作用,其定位于有丝分裂染色体上,具有精细的特异性:(i) MCAP-染色体关联在组蛋白H3磷酸化和早期染色体凝聚开始后变得明显;(ii)在异染色质的着丝粒中缺失MCAP。支持MCAP在G(2)/M转变中的作用,微量注射抗MCAP抗体进入HeLa细胞核完全抑制进入有丝分裂,而不破坏正在进行的DNA复制。这些结果表明MCAP在有丝分裂过程中起着控制染色体动力学的作用。
We describe a novel nuclear factor called mitotic chromosome-associated protein (MCAP), which belongs to the poorly understood BET subgroup of the bromodomain superfamily. Expression of the 200-kDa MCAP was linked to cell division, as it was induced by growth stimulation and repressed by growth inhibition. The most notable feature of MCAP was its association with chromosomes during mitosis, observed at a time when the majority of nuclear regulatory factors were released into the cytoplasm, coinciding with global cessation of transcription. Indicative of its predominant interaction with euchromatin, MCAP localized on mitotic chromosomes with exquisite specificity: (i) MCAP-chromosome association became evident subsequent to the initiation of histone H3 phosphorylation and early chromosomal condensation; and (ii) MCAP was absent from centromeres, the sites of heterochromatin. Supporting a role for MCAP in G(2)/M transition, microinjection of anti-MCAP antibody into HeLa cell nuclei completely inhibited the entry into mitosis, without abrogating the ongoing DNA replication. These results suggest that MCAP plays a role in a process governing chromosomal dynamics during mitosis.