| Inhibitor of DNA-binding/Differentiation (ID) proteins are a family of proteins that function to repress the activity of basic helix-loop-helix (bHLH) transcription factors. There are four known ID proteins in humans (ID1-4), all of which contain a helix-loop-helix domain but lack a basic DNA binding domain. Heterodimerization with bHLH transcription factors therefore functions to sequester bHLH proteins and prevent their binding to DNA. ID proteins play important functional roles in development, primarily by inhibiting premature differentiation of stem/progenitor cells. ID3 plays an important role in immune system development where it has been shown to repress E2A-mediated differentiation of T cells. Studies in mouse models have shown that homozygous deletion of ID3 disrupts regulatory T cell differentiation and leads to development of γδ T cell lymphoma. Outside of the hematopoietic compartment, ID3 was shown to repress MyoD, implicating 3 in TGFβ-mediated muscle repair. Similarly, research studies have shown that ID3 suppresses p21 in colon cancer cells, a function that is purported to promote the self-renewal capacity of putative cancer-initiating cells. |
