遗传 ›› 2015, Vol. 37 ›› Issue (1): 17-24.doi: 10.16288/j.yczz.2015.01.003

• 综述 • 上一篇    下一篇

Twist2的生物学功能及其分子机制

赵承孝1, 2, 3, 杨泽1, 2   

  1. 1. 卫生部北京医院,卫生部老年医学研究所医学遗传室,北京 100730;
    2. 北京协和医学院研究生院,北京 100730;
    3. 山西医科大学药学院,太原 030001
  • 收稿日期:2014-07-09 修回日期:2014-08-05 出版日期:2015-01-20 发布日期:2015-01-20
  • 通讯作者: 杨泽,教授,博士生导师,研究方向:遗传学。E-mail: yang_ze@sina.com E-mail:yang_ze@sina.com
  • 作者简介:赵承孝,博士研究生,专业方向:遗传学。Tel: 010-58115043,E-mail: zhaocx6@163.com
  • 基金资助:
    卫计委卫生行业科研专项(编号:201302008),科技部十二五项目(编号:2012BAI10B01)和国家自然科学基金项目(编号:81370445, 81241082)资助

Biological function and molecular mechanism of Twist2

Chengxiao Zhao1, 2, 3, Ze Yang1, 2   

  1. 1. Institute of Geriatrics, Chinese Ministry of Health, Beijing Hospital, Beijing 100730, China; 2. Graduate School of Peking Union Medical College, Beijing 100730, China; 3. School of Pharmaceutical, Shanxi Medical University, Taiyuan 030001, China
  • Received:2014-07-09 Revised:2014-08-05 Online:2015-01-20 Published:2015-01-20

摘要: 碱性螺旋-环-螺旋(Basic helix-loop-helix protein,bHLH)家族成员Twist2对间质细胞系的发生和发育起转录调节作用,经直接或间接机制发挥分子开关功能,从而激活或抑制靶基因。Twist2能直接结合DNA上 E-box保守序列,招募共激活物或抑制剂;能与E蛋白调节因子发生蛋白-蛋白相互作用,干扰激活或抑制功能。Twist2无义突变导致Setleis综合征。对Twist2的早期研究多集中在骨骼发育,随后在多种肿瘤中发现其有表达差异,研究表明Twist2在肿瘤的上皮-间质转化(Epithelial-mesenchymal transition,EMT)中发挥着重要作用。Twist2参与了多条通路的调控,其调控作用的发挥受到时空表达、磷酸化、二聚化和细胞定位的调节,在机体的正常发育、体内平衡和疾病发生机制中研究Twist2的作用显得尤为重要。文章对Twist2在成骨分化、肿瘤形成和EMT中的作用及其分子机制进行综述,以便帮助了解Twist2的生物学功能,为进一步在疾病的诊断、发展、以及治疗等方面的转化应用研究提供依据。

关键词: Twist2, 成骨, 肿瘤, 上皮间质转化, 机制

Abstract: Twist2, one of the basic helix-loop-helix protein (bHLH) family members, is responsible for the transcriptional regulation in mesenchymal cell lineages during its development. Twist2 functions as a molecular switch to activate or repress target genes by direct or indirect mechanisms. Twist2 can directly bind with conserved E-box on DNA sequence, to recruit co-activators or repressors, and interfere with the activation or inhibition function through protein-protein interactions with E-protein modulators. Nonsense mutations of Twist2 cause Setleis syndrome. Early research on Twist2 focused on osteogenesis, and then expression differences were found in a wide variety of tumors. Further studies showed that Twist2 plays an important role in cancer epithelial-mesenchymal transition (EMT). Regulation function of Twist2 is controlled by temporal and spatial expression, phosphorylation, dimerization and cell positioning adjustment. The involvement of Twist2 in a broad spectrum of regulatory pathways highlights the importance of understanding its role in normal development, homeostasis and disease. In this review, we summarize the role of Twist2 in osteogenesis differentiation, tumor formation and EMT, and its molecular mechanism. It is helpful to have a thorough understanding of the biological functions of Twist2, and facilitate the transformation and application in diagnosis, development and therapy.

Key words: Twist2, osteogenesis, tumor, epithelial-mesenchymal transition, mechanism