Inhibitor of differentiation protein-2 (is2) is a dominant negative helix-loop-helix (HLH) protein, and a positive regulator of proliferation, in various cells.
It has been known for several years that depletion of the dominant negative helix-loop-helix protein Id1 in mice leads to a failure of tumor angiogenesis and consequently a significant delay in tumor growth [5], [10].
While inhibitor of DNA binding 3, dominant negative helix-loop-helix protein (ID3) and v-myc myelocytomatosis viral oncogene homolog (avian) (MYC) were down-regulated.
Kulterer et al. [ 64] identified the expression of ID4 (encoding inhibitor of DNA binding dominant negative helix-loop-helix protein), CRYAB (alpha-crystallin B chain), and SORT1 (sortilin) in osteogenic differentiation of MSCs.
Additionally, loss of FAS led to down-regulation of ID2 and ID3, which are dominant negative helix-loop-helix (HLH) proteins that bind SREBP 1c and functionally repress FAS promoter activity [ 21].
Moreover, a reciprocal pattern of expression across outcome groups was observed for the dominant negative helix-loop-helix protein-encoding gene inhibitor of DNA-binding 3 (ID3) (online supplementary figure S4G), consistent with its putative regulatory role in STAT3 signalling.
ID2 (inhibitor of DNA binding 2, dominant negative helix-loop-helix binding protein), which was found to be pro-apoptotic in osteosarcoma cells [ 80], was exclusively induced in parental cells.
In addition, genes that were altered in response to DMOG but not to hypoxia included increased ephrin B2, reduced inhibitor of DNA-binding 3, dominant negative helix-loop-helix protein, neuropillin 2 and CCL-2, demonstrating that the effects of DMOG and hypoxia are not interchangeable.
The Ingenuity Pathway analysis of the selected genes from our microarray data showed that the oncogene Jun is involved in the expression of hairy and enhancer of split 1 (Hes1) in Rat1a cells [ 40], which is reported to interact with a dominant negative helix-loop-helix protein called inhibitor of DNA binding 4 (ID4) [ 41].
S200 phosphorylation is predicted to displace a negative regulatory helix causing autophosphorylation on the known MEK activatory residues, S218 and S222.
