Grouping transcription factors (TFs) by structural domain has been extremely useful. In some instances the DNA-binding domain provides clues to their function. Homeodomain-containing TFs (>250 discovered) are often associated with developmental processes, and those in the interferon regulatory factor family are generally associated with triggering immune responses against viral infections The homeodomain in DNA is defined by a 180 bp homeobox region encoding a helix–turn–helix DNA-binding[1]. Nkx2.5 is an important member of the family of homeobox-containing TFs. This transcription factor functions in heart formation and development. Mutations in this gene cause atrial septal defect with atrioventricular conduction defect, and also tetralogy of Fallot, which are both heart malformation diseases[2].
Shz-1 (Axon 1701) has the ability to mediate stem cell differentiation for the treatment of myocardial infarction and heart failure. It triggers cardiac mRNA and protein expression of the signature gene Nkx2.5, one of the earliest lineage-restricted genes to be expressed in cardiovascular progenitor cells, in a variety of embryonic and adult stem/progenitor cells, including human mobilized peripheral blood mononuclear cells (M-PBMCs)[3]. The exact mechanisms of gene activation and stem cell differentiation remain unclear.