Inhibitor of DNA Binding Protein 4 (ID4)

Transcription factors containing a basic helix-loop-helix (bHLH) motif regulate expression of tissue-specific genes in a number of mammalian and insect systems. DNA-binding activity of the bHLH proteins is dependent on formation of homo- and/or heterodimers. Dominant-negative HLH proteins encoded by Id-related genes, such as ID4, also contain the HLH-dimerization domain but lack the DNA-binding basic domain. Consequently, Id proteins inhibit binding to DNA and transcriptional transactivation by heterodimerization with bHLH proteins. ID4 was silenced by promoter methylation in the majority of human leukemias examined, but not in normal bone marrow, normal lymphocytes, or other tumor types. Transfection of mouse Id4 into a mouse lymphoid tumor inhibited cell growth in vitro and in SCID mice in vivo.