遗传
遺傳
유전
HEREDITAS(BEIJING)
2015年
1期
17-24
,共8页
Twist2%成骨%肿瘤%上皮间质转化%机制
Twist2%成骨%腫瘤%上皮間質轉化%機製
Twist2%성골%종류%상피간질전화%궤제
Twist2%osteogenesis%tumor%epithelial-mesenchymal transition%mechanism
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。
堿性螺鏇–環–螺鏇(Basic helix-loop-helix protein，bHLH)傢族成員Twist2對間質細胞繫的髮生和髮育起轉錄調節作用，經直接或間接機製髮揮分子開關功能，從而激活或抑製靶基因。Twist2能直接結閤DNA上 E-box保守序列，招募共激活物或抑製劑；能與E蛋白調節因子髮生蛋白–蛋白相互作用，榦擾激活或抑製功能。Twist2無義突變導緻Setleis綜閤徵。對Twist2的早期研究多集中在骨骼髮育，隨後在多種腫瘤中髮現其有錶達差異，研究錶明 Twist2在腫瘤的上皮–間質轉化(Epithelial-mesenchymal transition，EMT)中髮揮著重要作用。Twist2參與瞭多條通路的調控，其調控作用的髮揮受到時空錶達、燐痠化、二聚化和細胞定位的調節，在機體的正常髮育、體內平衡和疾病髮生機製中研究 Twist2的作用顯得尤為重要。文章對 Twist2在成骨分化、腫瘤形成和EMT中的作用及其分子機製進行綜述，以便幫助瞭解 Twist2的生物學功能，為進一步在疾病的診斷、髮展、以及治療等方麵的轉化應用研究提供依據。
감성라선–배–라선(Basic helix-loop-helix protein，bHLH)가족성원Twist2대간질세포계적발생화발육기전록조절작용，경직접혹간접궤제발휘분자개관공능，종이격활혹억제파기인。Twist2능직접결합DNA상 E-box보수서렬，초모공격활물혹억제제；능여E단백조절인자발생단백–단백상호작용，간우격활혹억제공능。Twist2무의돌변도치Setleis종합정。대Twist2적조기연구다집중재골격발육，수후재다충종류중발현기유표체차이，연구표명 Twist2재종류적상피–간질전화(Epithelial-mesenchymal transition，EMT)중발휘착중요작용。Twist2삼여료다조통로적조공，기조공작용적발휘수도시공표체、린산화、이취화화세포정위적조절，재궤체적정상발육、체내평형화질병발생궤제중연구 Twist2적작용현득우위중요。문장대 Twist2재성골분화、종류형성화EMT중적작용급기분자궤제진행종술，이편방조료해 Twist2적생물학공능，위진일보재질병적진단、발전、이급치료등방면적전화응용연구제공의거。
Twist2, one of the basic helix-loop-helix protein (bHLH) family members, is responsible for the tran-scriptional 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). Reg-ulation 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 im-portance 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.
