ID signaling (Homo sapiens)

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The Inhibitor of DNA binding (ID) proteins belong to the class V HLH family of transcription factors. Four ID proteins (ID 1-4) are known in humans.Unlike the basic HLH (bHLH) transcription factors, ID proteins lack the basic DNA binding region. They can heterodimerize with class I bHLH transcription factors to form inactive complexes. They thus act as dominant negative inhibitors of the class I bHLH transcription factors. They are also capable of regulating the activity of class II HLH transcription factors. Since, class I and II HLH proteins regulate the expression of cell type-specific genes and differentiated phenotype, ID proteins are thought to regulate the cross-talk between the pathways involved in cell growth and differentiation.

Aberrant expression of ID proteins are found in many primary tumors and are found to regulate many steps in cancer progression including Neo-angiogenesis, invasion and migration, proliferation and growth, cell-cell interaction and differentiation. These include head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, melanoma, hepatocellular carcinonoma, pancreatic cancer, Ovarian cancer, cervical cancer, breast cancer and prostate cancer.

Among the transcription factors that ID proteins associate with are the Ets family members (ELKs) and paired box family (PAXs). They can also bind to the retiboblastoma and retinoblastoma-like proteins (RBLs), which are thought to be tumor suppressors. IDs can also be phosphorylated by CDK2.

NetPath (http://www.netpath.org) is a collaborative effort between PandeyLab at Johns Hopkins University (http://pandeylab.igm.jhmi.edu) and Institute of Bioinformatics (http://www.ibioinformatics.org). This version of the pathway is available at NetSlim (http://www.netpath.org/netslim). If you use this pathway, please cite the NetPath website.