国际著名学术期刊《血液》（Blood）近日在线发表了南开大学生命科学学院周军教授课题组的最新研究成果，该成果发现了微管结合蛋白CYLD在调控血管新生过程中的重要作用。
血管新生是人体内许多正常生理活动的基础，对于肿瘤的生长和转移也非常重要。血管新生是一个受到严密调控的多步骤过程，其中血管内皮细胞的迁移是关键一环。周军课题组博士生高金珉等人前期的研究发现，CYLD通过其CAP-Gly结构域与微管细胞骨架相互作用，调节微管的组装和稳定性，从而有利于细胞的迁移，2008年发表在《生物化学杂志》（Journal of Biological Chemistry）上。
在本项研究中，高金珉等人在他们前期工作的基础上，发现CYLD通过对血管内皮细胞中微管的动态性进行精细调节，刺激Rac1的活化，介导血管内皮细胞的极化和迁移，从而促进新血管的形成。该项研究发现了CYLD调节血管新生过程的一个新功能，加深了对微管及其相关蛋白功能和调控机制的理解。该项工作得到国家自然科学基金、科技部重大科学研究计划及天津市科委项目的资助。
《血液》发表论文摘要（英文）
Blood First Edition Paper, prepublished online March 1, 2010; DOI 10.1182/blood-2009-10-248526.
Submitted October 13, 2009; accepted February 7, 2010.
CYLD regulates angiogenesis by mediating vascular endothelial cell migration
Jinmin Gao, Lei Sun, Lihong Huo, Min Liu, Dengwen Li and Jun Zhou*
1 Dept. of Genetics and Cell Biology, Key Lab of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China
* Corresponding author; email: junzhou@nankai.edu.cn
Abstract
Cylindromatosis (CYLD) is a deubiquitinase that was initially identified as a tumor suppressor and has recently been implicated in diverse normal physiological processes. In this study, we have investigated the involvement of CYLD in angiogenesis, the formation of new blood vessels from preexisting ones. We find that knockdown of CYLD expression significantly impairs angiogenesis in vitro in both matrigel-based tube formation assay and collagen-based three-dimensional capillary sprouting assay. Disruption of CYLD also remarkably inhibits angiogenic response in vivo, as evidenced by diminished blood vessel growth into the angioreactors implanted in mice. Mechanistic studies reveal that CYLD regulates angiogenesis by mediating the spreading and migration of vascular endothelial cells. Silencing of CYLD dramatically decreases microtubule dynamics in endothelial cells and inhibits endothelial cell migration by blocking the polarization process. Furthermore, we identify Rac1 activation as an important factor contributing to the action of CYLD in regulating endothelial cell migration and angiogenesis. Our findings thus uncover a previously unrecognized role for CYLD in the angiogenic process and provide a novel mechanism for Rac1 activation during endothelial cell migration and angiogenesis.
