TWIST 1 ( twist homolog 1 ( Drosophila ) )

The 20.9 kDa protein encoded by TWIST1 gene is a highly conserved transcription factor that belongs to the family of basic helix-loop-helix (bHLH) proteins. In vertebrates, it is involved in embryonic development through the regulation of epithelial-mesenchymal transitions (EMT) during neural crest migration, also it regulates mesoderm determination, myogenesis, and morphogenesis (Hebrok et al., 1994; Chen et al., 1995). Additionally, TWIST1 is involved in the negative regulation of cellular determination and in the differentiation of several lineages including myogenesis, osteogenesis (Bialek et al., 2004), and neurogenesis (Soo et al., 2002). Inhibits myogenesis by sequestrating E proteins, avoiding trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. Also represses expression of proinflammatory cytokines such as TNFA and IL1B (Barnes et al., 2009). Mutations in this gene have been found in patients with Saethre-Chotzen syndrome (Howard et al., 1997). TWIST1 has been suggested to be oncogenic, contributing to metastasis through its involvement in EMT regulation (Yang et al., 2004). In addition, TWIST1 is overexpressed in multiple tumor types, and it is usually associated with poor prognosis. In mammals, there are two Twist-like proteins, TWIST1 and TWIST2 that share high structural homology (Li et al., 1995; Wolf et al., 1991). It is thought that during osteoblast development TWIST2 or Dermo1 may inhibit osteoblast maturation and maintain cells in a preosteoblast phenotype [provided by RefSeq]. Interestingly, TWIST2 has a pro-oncogenic role in human cancer (Ansieau et al., 2008). Structure TWIST1 protein contains a helix-loop-helix DNAbinding domain. Efficient DNA binding requires dimerization with another bHLH protein.