Id2, like other ID proteins, lacks a DNA-binding domain but contains a helix-loop-helix (HLH) domain. This domain allows Id2 to form heterodimers with bHLH transcription factors, preventing them from binding to DNA and thus inhibiting their function . This mechanism is crucial in various biological processes, including cell cycle regulation, differentiation, and development.
Id2 has been implicated in the regulation of cancer stem cells (CSCs) in head and neck squamous cell carcinomas (HNSCCs). Research has shown that Id2 expression is higher in HNSCC cells with stemness characteristics compared to differentiated cells . Overexpression of Id2 enhances proliferation, self-renewal, and expression of stemness markers like CD44 in HNSCC cells. Conversely, silencing Id2 reduces these stemness traits, indicating its potential as a therapeutic target for cancer treatment .
The study of Id2 extends beyond cancer research. Its role in negatively regulating cell differentiation makes it a significant protein in developmental biology and regenerative medicine. Researchers are exploring various methods to modulate Id2 activity, including the use of small-molecule inhibitors to disrupt its interaction with bHLH transcription factors .