About ID / Inhibitor of DNA Binding:
Inhibitor of DNA-binding/differentiation proteins, also known as ID proteins, are 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. However, they lack the basic DNA-binding domain, thus regulating bHLH transcription factors when they heterodimerize with bHLH proteins.
ID proteins regular development where they function to prevent premature differentiation of stem cells. ID proteins regulate the timing of differentiation of stem cells during development by inhibiting E-protein dimer formations that cause differentiation. ID proteins also promote cell cycle progression, delaying senescence, and assist with cell migration.
Inappropriate regulation of ID proteins in differentiated cells can contribute to tumorigenesis, also known as carcinogenesis or the formation of cancer where normal cells are transformed into cancer cells. When ID proteins are overexpressed, it enhances cell proliferation and cells become insensitive to growth factor depletion.
Inhibitor of DNA Binding Subtypes
Humans express four types of Id proteins called ID1, ID2, ID3, and ID4.
Publications have shown that ID1 can be used to mark endothelial progenitor cells which are critical to tumour growth and angiogenesis. Targeting ID1 can result in decreased tumour growth which could potentially be used to design a novel cancer therapy.
Studies have recorded the phenotypic effects of each ID gene when knocked out in mice:
●A knockout of ID1 showed a defect in T-cell migration.
●A knockout of ID2 showed that 25% of mice died perinatally while the born lacked lymph nodes and showed defects in mammary proliferation.
●A knockout of ID3 showed normal development, but they had a defect in B-cell proliferation.
●A knockout of ID4 showed neural defects and premature differentiation.
●A knockout of both ID1 and ID3 resulted in embryonic lethality due to brain haemorrhaging and abnormalities in cardiac development.