Dey A, Ellenberg J, Farina A, Coleman A E, Maruyama T, Sciortino S, Lippincott-Schwartz J, Ozato K
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2753, USA.
Mol Cell Biol. 2000 Sep;20(17):6537-49. doi: 10.1128/MCB.20.17.6537-6549.2000.
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.
我们描述了一种名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了解较少的BET亚组。200 kDa的MCAP的表达与细胞分裂相关，因为它在生长刺激时被诱导，在生长抑制时被抑制。MCAP最显著的特征是在有丝分裂期间与染色体相关联，这一现象在大多数核调节因子释放到细胞质中时被观察到，同时伴随着全局转录的停止。表明其与常染色质的主要相互作用，MCAP以极高的特异性定位于有丝分裂染色体上：（i）MCAP与染色体的关联在组蛋白H3磷酸化开始和早期染色体凝聚之后变得明显；（ii）着丝粒（异染色质位点）上没有MCAP。支持MCAP在G(2)/M转换中的作用，将抗MCAP抗体显微注射到HeLa细胞核中完全抑制了进入有丝分裂的过程，而不影响正在进行的DNA复制。这些结果表明MCAP在有丝分裂期间控制染色体动态的过程中发挥作用。
