Fig. 1.

TWIST1 is a highly conserved bHLH class transcription factor with multiple functions. a TWIST1 functions in normal development and in small populations of adult stem cells, where it assists in wound healing. When reactivated in cancers, TWIST1 activates a transcriptional and protein binding program giving rise to EMT, and thus to metastases. Many studies have also linked re-expression of TWIST1 to the acquisition of drug resistance and an increase in stemness. Functions in normal tissue are shown in green; in cancer, in red. b Human TWIST1 protein is 202 amino acids in length, with the N-terminal half of the protein being largely disodered The C-terminal half consists of the basic DNA binding domain (orange), helix-loop-helix dimerization domain (yellow), and the Twist box or WR domain (blue), which has been shown to be a transactivation domain. c The WR domain is especially well conserved throughout evolution, with 100% identity between human, mouse, and frog. The central residues appearing in green are present in all organisms listed, including Drosophila, and for this reason, residues were selected for mutation