ID signaling

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 retinoblastoma and retinoblastoma-like proteins (RBLs), which are thought to be tumor suppressors. IDs can also be phosphorylated by CDK2. Please access this pathway at [http://www.netpath.org/netslim/id_pathway.html NetSlim] database. If you use this pathway, please cite following paper: Kandasamy, K., Mohan, S. S., Raju, R., Keerthikumar, S., Kumar, G. S. S., Venugopal, A. K., Telikicherla, D., Navarro, J. D., Mathivanan, S., Pecquet, C., Gollapudi, S. K., Tattikota, S. G., Mohan, S., Padhukasahasram, H., Subbannayya, Y., Goel, R., Jacob, H. K. C., Zhong, J., Sekhar, R., Nanjappa, V., Balakrishnan, L., Subbaiah, R., Ramachandra, Y. L., Rahiman, B. A., Prasad, T. S. K., Lin, J., Houtman, J. C. D., Desiderio, S., Renauld, J., Constantinescu, S. N., Ohara, O., Hirano, T., Kubo, M., Singh, S., Khatri, P., Draghici, S., Bader, G. D., Sander, C., Leonard, W. J. and Pandey, A. (2010). NetPath: A public resource of curated signal transduction pathways. <i>Genome Biology</i>. 11:R3.

DNA结合抑制因子（ID）蛋白属于V HLH转录因子家族。在人类中已知存在四种ID蛋白（ID 1-4）。与基本HLH（bHLH）转录因子不同，ID蛋白缺少基本的DNA结合区域。它们可以与I类bHLH转录因子异源二聚化，形成非活性复合物。因此，它们作为I类bHLH转录因子的显性负抑制因子发挥作用。此外，它们还能够调节II类HLH转录因子的活性。由于I类和II类HLH蛋白调节细胞特异性基因的表达和分化表型，因此ID蛋白被认为调节参与细胞生长和分化的通路之间的相互作用。ID蛋白的异常表达在许多原发性肿瘤中均有发现，并且发现它们调节癌症进展的许多步骤，包括新生血管生成、侵袭和转移、增殖和生长、细胞间相互作用和分化。这些包括头颈鳞状细胞癌、食管鳞状细胞癌、黑色素瘤、肝细胞癌、胰腺癌、卵巢癌、宫颈癌、乳腺癌和前列腺癌。与ID蛋白相互作用的转录因子包括Ets家族成员（ELKs）和成对盒家族（PAXs）。它们还可以与视网膜母细胞瘤及其类似蛋白（RBLs）结合，这些蛋白被认为具有肿瘤抑制功能。ID蛋白还可以被CDK2磷酸化。请访问[http://www.netpath.org/netslim/id_pathway.html NetSlim]数据库。若使用此通路，请引用以下论文：Kandasamy, K.，Mohan, S. S.，Raju, R.，Keerthikumar, S.，Kumar, G. S. S.，Venugopal, A. K.，Telikicherla, D.，Navarro, J. D.，Mathivanan, S.，Pecquet, C.，Gollapudi, S. K.，Tattikota, S. G.，Mohan, S.，Padhukasahasram, H.，Subbannayya, Y.，Goel, R.，Jacob, H. K. C.，Zhong, J.，Sekhar, R.，Nanjappa, V.，Balakrishnan, L.，Subbaiah, R.，Ramachandra, Y. L.，Rahiman, B. A.，Prasad, T. S. K.，Lin, J.，Houtman, J. C. D.，Desiderio, S.，Renauld, J.，Constantinescu, S. N.，Ohara, O.，Hirano, T.，Kubo, M.，Singh, S.，Khatri, P.，Draghici, S.，Bader, G. D.，Sander, C.，Leonard, W. J. 和 Pandey, A.（2010）. NetPath: 一个公共的信号转导通路资源。《基因组生物学》。11：R3。