Cai Juanliang, Jabs Ethylin Wang
Institute of Genetic Medicine, Center for Craniofacial Development and Disorders, The Johns Hopkins University, Baltimore, MD 21205, USA.
Bioessays. 2005 Nov;27(11):1102-6. doi: 10.1002/bies.20313.
Saethre-Chotzen syndrome (SCS), a human autosomal dominant condition with limb defects and craniosynostosis, is caused by haploinsufficiency of TWIST1, a basic helix-loop-helix (bHLH) transcription factor. Until recently, the molecular pathogenesis of the limb defects in SCS has not been well understood. Now, Firulli et al.1 show in mouse and chick that ectopic expression of a related bHLH protein, Hand2, results in phenocopies of the limb defects caused by Twist1 loss-of-function mutations. These two proteins interact in a dosage-dependent antagonistic manner, and both can be regulated through phosphorylation at conserved helix I amino acid residues. These findings provide an important link between the misregulation of Twist1 dimerization and the limb phenotypes observed in SCS.
塞特勒-乔岑综合征（SCS）是一种具有肢体缺陷和颅缝早闭的人类常染色体显性疾病，由基本螺旋-环-螺旋（bHLH）转录因子TWIST1的单倍剂量不足引起。直到最近，SCS中肢体缺陷的分子发病机制仍未得到很好的理解。现在，菲鲁利等人在小鼠和小鸡中发现，相关bHLH蛋白Hand2的异位表达会导致由Twist1功能丧失突变引起的肢体缺陷表型模拟。这两种蛋白质以剂量依赖性拮抗方式相互作用，并且两者都可以通过保守的螺旋I氨基酸残基处的磷酸化进行调节。这些发现为Twist1二聚化失调与SCS中观察到的肢体表型之间提供了重要联系。
