Inhibitor of DNA-binding protein

Inhibitor of DNA-binding/differentiation proteins, also known as Id proteins comprise a family of proteins that heterodimerize with basic helix-loop-helix (bHLH) transcription factors to inhibit DNA binding of bHLH proteins.[1] Id proteins also contain the HLH-dimerization domain but lack the basic DNA-binding domain and thus negatively regulate bHLH transcription factors when they heterodimermize with bHLH proteins.[2]

Function

ID proteins are key regulators of development where they function to prevent premature differentiation of stem cells.[3] In contrast, inappropriate regulation of ID proteins in differentiated cells can contribute to tumorigenesis.[4][5][6] Finally expression of ID proteins in neurons halts neuron axon growth and allows elongation of neurons.[7]

Subtypes

Humans express four types of Id proteins (called ID1, ID2, ID3, and ID4).

A recent publication in Cancer Research (August 2010) has shown that ID1 can be used to mark Endothelial Progenitor Cells which are critical to tumour growth and angiogenesis. This publication has demonstrated that targeting ID1 resulted in decreased tumour growth. Therefore, ID1 could be used to design a novel cancer therapy.[8]

References

  1. ↑ Perk J, Iavarone A, Benezra R (August 2005). "Id family of helix-loop-helix proteins in cancer". Nat. Rev. Cancer 5 (8): 603–14. doi:10.1038/nrc1673. PMID 16034366.
  2. ↑ Pagliuca A, Bartoli PC, Saccone S, Della Valle G, Lania L (May 1995). "Molecular cloning of ID4, a novel dominant negative helix-loop-helix human gene on chromosome 6p21.3-p22". Genomics 27 (1): 200–3. doi:10.1006/geno.1995.1026. PMID 7665172.
  3. ↑ Yokota Y (December 2001). "Id and development". Oncogene 20 (58): 8290–8. doi:10.1038/sj.onc.1205090. PMID 11840321.
  4. ↑ Benezra R, Rafii S, Lyden D (December 2001). "The Id proteins and angiogenesis". Oncogene 20 (58): 8334–41. doi:10.1038/sj.onc.1205160. PMID 11840326.
  5. ↑ Lasorella A, Uo T, Iavarone A (December 2001). "Id proteins at the cross-road of development and cancer". Oncogene 20 (58): 8326–33. doi:10.1038/sj.onc.1205093. PMID 11840325.
  6. ↑ Zebedee Z, Hara E (December 2001). "Id proteins in cell cycle control and cellular senescence". Oncogene 20 (58): 8317–25. doi:10.1038/sj.onc.1205092. PMID 11840324.
  7. ↑ Iavarone A, Lasorella A (December 2006). "ID proteins as targets in cancer and tools in neurobiology". Trends Mol Med 12 (12): 588–94. doi:10.1016/j.molmed.2006.10.007. PMID 17071138.
  8. ↑ Mellick As, Plummer PN (2010). "Using the Transcription Factor Inhibitor of DNA Binding 1 to Selectively Target Endothelial Progenitor Cells Offers Novel Strategies to Inhibit Tumor Angiogenesis and Growth". Cancer Research 70 (18): 7273–7282. doi:10.1158/0008-5472.CAN-10-1142. PMC 3058751. PMID 20807818.

External links


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