Oncogenic Transcription Factors: Target Genes

Luiz F Zerbini, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA

Published online: September 2007

DOI: 10.1002/9780470015902.a0006049

An elevated percentage of oncogenes and tumour suppressor genes encode transcription factors. Deregulated expression of transcription factors plays critical roles in different diseases including cancer. Furthermore, the majority of oncogenic signalling pathways converge on sets of transcription factors that ultimately control gene expression patterns resulting in disease progression. Since the expression and activities of these transcription factors are tightly regulated, they represent highly desirable points of therapeutical interference to validate them as drug targets.

Keywords: transcription factors; apoptosis; cancer; oncogene; cell cycle

Figure 1. Transcription factor (TF) activation and signalling pathway in cancer. Transcription factors activity is triggered by genetic alterations such as point mutations, insertions, deletions, chromosomal translocations and amplifications in the tumour cell's DNA. These events lead to transcription factor aberrant expression and abnormal activity and activate an intracellular signalling cascade resulting in the nuclear translocation and transcriptional activation of target genes involved in many aspects of tumorigenesis, inflammation and proliferation and survival of cancer cells.
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 References
    Arvand A and Denny CT (2001) Biology of EWS/ETS fusions in Ewing's family tumors. Oncogene 20: 5747–5754.
    Blume-Jensen P and Hunter T (2001) Oncogenic kinase signalling. Nature 411: 355–365.
    Darnell JE Jr (2002) Transcription factors as targets for cancer therapy. Nature Reviews Cancer 2: 740–749.
    Dittmer J (2003) The biology of the Ets 1 proto-oncogene. Molecular Cancer 2: 29.
    Duterque-Coquillaud M, Niel C, Plaza S and Stehelin D (1993) New human erg isoforms generated by alternative splicing are transcriptional activators. Oncogene 8: 1865–1873.
    Eferl E and Wagner EF (2003) AP-1: a double-edged sword in tumorigenesis. Nature Reviews Cancer 3: 859–868.
    Green DR and Evan GI (2002) A matter of life and death. Cancer Cell 1: 19–30.
    Ichikawa H, Shimizu K, Katsu R and Ohki M (1999) Dual transforming activities of the FUS (TLS)-ERG leukemia fusion protein conferred by two N-terminal domains of FUS (TLS). Molecular Cell Biology 19: 7639–7650.
    Knoop LL and Baker SJ (2001) EWS/FLI alters 5¢-splice site selection. Journal of Biological Chemistry 276: 22317–22322.
    Koehler AN, Shamji AF and Schreiber SL (2003) Discovery of an inhibitor of a transcription factor using small molecule microarrays and diversity-oriented synthesis. Journal of the American Chemical Society 125: 8420–8421.
    Libermann TA and Zerbini LF (2006) Targeting transcription factors for cancer gene therapy. Review of Current Gene Therapy 6: 17–33.
    Obika S, Reddy SY and Bruice TC (2003) Sequence specific DNA binding of Ets-1 transcription factor: molecular dynamics study on the Ets domain–DNA complexes. Journal of Molecular Biology 331: 345–359.
    Oettgen P, Alani RM, Barcinski MA et al. (1997) Isolation and characterization of a novel epithelium-specific transcription factor, ESE-1, a member of the ets family. Molecular Cell Biology 17: 4419–4433.
    Oikawa T (2004) ETS transcription factors: possible targets for cancer therapy. Cancer Science 95: 626–633.
    Pufall MA, Lee GM, Nelson ML et al. (2005) Variable control of Ets-1 DNA binding by multiple phosphates in an unstructured region. Science 309: 142–145.
    Ravi R and Bedi A (2004) NF-B in cancer – a friend turned foe. Nature 411: 342–348.
    Seth A and Watson DK (2005) ETS transcription factors and their emerging roles in human cancer. European Journal of Cancer 41(16): 2462–2478.
    Strausberg RL, Simpson AJ, Old LJ and Riggins GJ (2004) Oncogenomics and the development of new cancer therapies. Nature 429: 469–474.
    Tomlins SA, Rhodes DR, Perner S et al. (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310: 644–648.
    Zerbini LF, Wang Y, Czibere A et al. (2004) NF- B-mediated repression of growth arrest- and DNA-damage-inducible proteins 45 and is essential for cancer cell survival. Proceedings of the National Academy of Sciences of the USA 101: 13618–13623.
 Further Reading
    Shoichet BK (2004) Virtual screening of chemical libraries. Nature 432: 862–865.

Related Sub-Topics:

Molecular Genetics of Common and Complex Disease | Cancer Genetics | Epigenetics and Disease | Epigenetics and Disease | Gene Expression Profiling of Genetic Disease | Transcriptional Regulation
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Article Title: Oncogenic Transcription Factors: Target Genes
 
How to Cite close
Zerbini, Luiz F(Sep 2007) Oncogenic Transcription Factors: Target Genes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006049]