Inhibitor of DNA-binding/differentiation proteins, also known as ID proteins comprise a family of proteins that heterodimerize with basic helix-loop-helix (bHLH) transcription factors to inhibit DNA binding of bHLH proteins. ID proteins also contain the HLH-dimerization domain but lack the basic DNA-binding domain and thus regulate bHLH transcription factors when they heterodimerize with bHLH proteins. The first helix-loop-helix proteins identified were named E-proteins because they bind to Ephrussi-box (E-box) sequences. In normal development, E proteins form dimers with other bHLH transcription factors, allowing transcription to occur. However, in cancerous phenotypes, ID proteins can regulate transcription by binding E proteins, so no dimers can be formed and transcription is inactive. E proteins are members of the class I bHLH family and form dimers with bHLH proteins from class II to regulate transcription. Four ID proteins exist in humans: ID1, ID2, ID3, and ID4. The ID homologue gene in Drosophila is called extramacrochaetae (EMC) and encodes a transcription factor of the helix-loop-helix family that lacks a DNA binding domain. EMC regulates cell proliferation, formation of organs like the midgut, and wing development. ID proteins could be potential targets for systemic cancer therapies without inhibiting the functioning of most normal cells because they are highly expressed in embryonic stem cells, but not in differentiated adult cells. Evidence suggests that ID proteins are overexpressed in many types of cancer. For example, ID1 is overexpressed in pancreatic, breast, and prostate cancers. ID2 is upregulated in neuroblastoma, Ewing’s sarcoma, and squamous cell carcinoma of the head and neck.
The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. The encoded protein has also been identified as the beta subunit of a heterodimeric transcription factor, hypoxia-inducible factor 1 (HIF1). A t(1;12)(q21;p13) translocation, which results in a TEL-ARNT fusion protein, is associated with acute myeloblastic leukemia. Three alternatively spliced variants encoding different isoforms have been described for this gene.
The breakpoint cluster region protein (BCR) also known as renal carcinoma antigen NY-REN-26 is a protein that in humans is encoded by the BCR gene. BCR is one of the two genes in the BCR-ABL fusion protein, which is associated with the Philadelphia chromosome. Two transcript variants encoding different isoforms have been found for this gene.
T-cell acute lymphocytic leukemia protein 1 is a protein that in humans is encoded by the TAL1 gene.
MYC proto-oncogene, bHLH transcription factor is a protein that in humans is encoded by the MYC gene which is a member of the myc family of transcription factors. The protein contains basic helix-loop-helix (bHLH) structural motif.
Transcription factor 3, also known as TCF3, is a protein that in humans is encoded by the TCF3 gene. TCF3 has been shown to directly enhance Hes1 expression.
DNA-binding protein inhibitor ID-2 is a protein that in humans is encoded by the ID2 gene.
Pre-B-cell leukemia transcription factor 1 is a protein that in humans is encoded by the PBX1 gene.
LIM domain only 2, also known as LMO2, RBTNL1, RBTN2, RHOM2, LIM Domain Only Protein 2, TTG2, and T-Cell Translocation Protein 2, is a protein which in humans is encoded by the LMO2 gene.
DNA-binding protein inhibitor ID-1 is a protein that in humans is encoded by the ID1 gene.
MAX is a gene that in humans encodes the MAX transcription factor.
DNA-binding protein inhibitor ID-3 is a protein that in humans is encoded by the ID3 gene.
PBX/Knotted 1 Homeobox 1 (PKNOX1) is a protein that in humans is encoded by the PKNOX1 gene.
Hepatic leukemia factor is a protein that in humans is encoded by the HLF gene.
Rhombotin-1 is a protein that in humans is encoded by the LMO1 gene.
ID4 is a protein coding gene. In humans, it encodes for the protein known as DNA-binding protein inhibitor ID-4. This protein is known to be involved in the regulation of many cellular processes during both prenatal development and tumorigenesis. This is inclusive of embryonic cellular growth, senescence, cellular differentiation, apoptosis, and as an oncogene in angiogenesis.
Protein ENL is a protein that in humans is encoded by the MLLT1 gene.
Pre-B-cell leukemia transcription factor 3 is a protein that in humans is encoded by the PBX3 gene.
Helix-loop-helix protein 1 is a protein that in humans is encoded by the NHLH1 gene.
T-cell acute lymphocytic leukemia 2, also known as TAL2, is a protein which in humans is encoded by the TAL2 gene.
