Transcriptional targeting

Chang YE et al. Microarray analysis identifies interferon-inducible genes and Stat-1 as major transcriptional targets of human papillomavims type 31. J Virol 2000 74 4174-4182. 

Most often, the ISH phase is done last because some antigens may be destroyed by the high temperature and protein digestion of ISH. Conversely, the antibodies used for immunocytochemistry may have some RNase carryover that will diminish transcript targets. The addition of RNase inhibitors, therefore, may be warranted (12). 

Wu L, Johnson M, Sato M. Transcriptionally targeted gene therapy to detect and treat cancer. Trends Mol Med 2003 9 421-9. 

Targeting DNA replication Targeting transcription Targeting translation Targeting mitosis/meiosis... 

An important transcriptional target of the p53 protein that can induce apoptosis is the bax gene. The Bax protein belongs to the family of Bcl-2 proteins (see 15.3.2) and has a proapototic effect. There is speculation that the p53-induced increase in Bax concentration leads to formation of ion pores in mitochondria and that cytochrome c is released into the cytosol via these pores. Cytochrome c then functions as a cofactor which, together with Apafl protein, activates procaspase 8 and initiates the apoptotic program. 

Expression of another set of genes establishes the right-left axis and characteristic asymmetries of the body.333-336 In the chick activin 2(3, also a member of the TGF-P family, as well as Nodal and Sonic hedgehog (Shh) participate in control. The gene Pitx2 is a downstream transcription target for this signaling cascade in vertebrates. 

Reynolds, P. N., Nicklin, S. A., Kaliberova, L., et al. Combined transductional and transcriptional targeting improves the specificity of transgene expression in vivo. Nature Biotechnol. 19 838-842, 2001. 

Numerous transcriptionally targeted replication-competent adenovimses and herpes viruses have been shown to be highly specific (up to 10,000-fold relative to nontarget cells) in cell culture experiments. In addition, animal models have demonstrated their safety and efficacy. It thus appears that the transcriptional targeting of viral replication holds some promise as a strategy for cancer gene therapy. 

S. Miyatake, A. Iyer, R. L. Martuza, and S. D. Rabkin, Transcriptional targeting of herpes simplex virus for cell-specific replication, J. Virol. 77 5124 (1997). 

Table 1 Summary of progress toward transcription-targeted therapeutics...

Okamoto K, Beach D. 1994. Cyclin G is a transcriptional target of the p53 tumor suppressor protein. EMBO J 13 4816 822. 

An important link exists between the pRb/E2F pathway, since ARF is one of the transcriptional targets of the E2F transcription factors. Furthermore, ARF is under transcriptional control by the transcription factor c-Myc, providing a link from c-Myc to the function of p53. 

Lu NZ, Cidlowski JA Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes. Mol Cell 2005 18 331-342. 

Haviv Y. S., van Houdt W. J., Lu B., et al. (2004) Transcriptional targeting in renal cancer cell lines via the human CXCR4 promoter. Mol Cancer Ther. 3, 687-91. 

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