Huhn S C, Liu J, Ye C, Lu H, Jiang X, Feng X, Ganesan S, White E, Shen Z
Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, New Jersey 08903, USA.
Department of Radiation Oncology, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
Oncogene. 2017 Aug 17;36(33):4750-4766. doi: 10.1038/onc.2017.92. Epub 2017 Apr 10.
Centrosomes together with the mitotic spindle ensure the faithful distribution of chromosomes between daughter cells, and spindle orientation is a major determinant of cell fate during tissue regeneration. Spindle defects are not only an impetus of chromosome instability but are also a cause of developmental disorders involving defective asymmetric cell division. In this work, we demonstrate BCCIP, especially BCCIPα, as a previously unidentified component of the mitotic spindle pole and the centrosome. We demonstrate that BCCIP localizes proximal to the mother centriole and participates in microtubule organization and then redistributes to the spindle pole to ensure faithful spindle architecture. We find that BCCIP depletion leads to morphological defects, disoriented mitotic spindles, chromosome congression defects and delayed mitotic progression. Our study identifies BCCIP as a novel factor critical for microtubule regulation and explicates a mechanism utilized by BCCIP in tumor suppression.
中心体与有丝分裂纺锤体共同确保染色体在子细胞间的准确分配,而纺锤体定向是组织再生过程中细胞命运的主要决定因素。纺锤体缺陷不仅是染色体不稳定的诱因,也是涉及不对称细胞分裂缺陷的发育障碍的原因。在这项研究中,我们证明了BCCIP,尤其是BCCIPα,是有丝分裂纺锤体极和中心体中一个此前未被识别的成分。我们证明BCCIP定位于母中心粒近端,参与微管组织,然后重新分布到纺锤体极以确保纺锤体结构的准确无误。我们发现BCCIP缺失会导致形态缺陷、有丝分裂纺锤体定向紊乱、染色体排列缺陷以及有丝分裂进程延迟。我们的研究确定BCCIP是一种对微管调节至关重要的新因子,并阐明了BCCIP在肿瘤抑制中所利用的机制。