摘要: |
锌指蛋白ZBTB20是ZBTB锌指蛋白亚家族的新成员, 与已知的BCL6和PLZF同源。通过基因打靶小鼠和疾病人群研究, 学者们发现ZBTB20在肝脏、胰岛、神经系统和免疫系统等多个器官与系统中具有重要生理学功能, 是个体发育、学习记忆、痛觉感受、糖脂代谢等正常生理过程所必需的调节分子。ZBTB20表达或功能异常可导致个体发育障碍, 与智障、肿瘤和代谢性疾病等多种重大疾病的病理生理过程密切相关。作为甲胎蛋白基因的主要转录抑制因子, ZBTB20在出生后肝脏甲胎蛋白基因的表达失活中发挥了关键性作用, 且与肝癌预后密切相关。人群中ZBTB20基因的缺失与多种肿瘤有关, 其点突变可导致Primrose综合征。本文就ZBTB20的生物学功能研究进展作一综述。 |
关键词: 锌指蛋白 ZBTB20 转录因子 生理与病理生理 基因打靶 |
DOI:10.3724/SP.J.1008.2015.00525 |
投稿时间:2015-03-12修订日期:2015-04-08 |
基金项目:国家杰出青年科学基金(31025013),国家自然科学基金重点项目(81130084),国家重点基础研究发展计划(“973”计划)(2012CB524904). |
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Biological functions of zinc finger protein ZBTB2: recent advance |
LIU Gan1,CHENLI Bin-ji1,XIE Zhi-fang2,ZHANG Wei-ping1* |
(1. Department of Pathophysiology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China; 2. Department of Cell Biology, College of Basic Medical Sciences, Second Military Medical University, Shanghai 200433, China *Corresponding author) |
Abstract: |
Zinc finger protein ZBTB20 is a novel member of the ZBTB zinc finger protein family and shares closest homology with BCL-6 and PLZF. Recent studies on genetically modified mice and patient cohort have revealed that ZBTB20 plays indispensable roles in multiple organs and systems, including the nervous system, liver, pancreatic islets, and immune system. ZBTB20 is an essential regulatory factor in a variety of physiological processes, such as ontogenesis, pain sensation, learning and memory, as well as glucose and lipid metabolism. Meanwhile, recent researches have also showed a close relationship between the abnormality or dysfunction of ZBTB20 and pathophysiological procedures of diseases, such as maldevelopment, mental retardation, tumors and metabolic disorders. As a key repressor governing AFP gene transcription, ZBTB20 exerts a great influence on the gene inactivation of liver AFP after birth and is closely related to the prognosis of hepatocellular carcinogenesis. In humans, the deletion of ZBTB20 is detected in diverse tumors and its point mutation leads to Primrose syndrome. This review summarizes the current knowledge concerning the biological functions of ZBTB20. |
Key words: zinc finger proteins ZBTB20 transcriptional factors physiology and pathophysiology gene targeting |