Sensitivity gene

Rodriguez, J. F., et al. (1988). Expression of the firefly luciferase gene in vaccinia virus a highly sensitive gene marker to follow virus dissemination in tissues of infected animals. Proc. Natl. Acad. Sci. USA 85 1667-1671. 

Y.-F. Tsay, J. L. Schroeder, K. A. Feidmann, and N. M. Crawford, A herbicide sensitive gene CHLI of Arahidopsis encodes a nitrate-inducible nitrate transporter. Cell 72 705 (1993). 

Rnorr V, Russ V, Allmendinger L, Ogris M, Wagner E (2008) Acetal linked oligoethy-lenimines for use as pH-sensitive gene carriers. Bioconjug Chem 19 1625-1634... 

All interferon-stimulated genes are characterized by the presence of an associated interferon-stimulated response element (ISRE). Signal transduction culminates in the binding of specific regulatory factors to the ISRE, which stimulates RNA polymerase Il-mediated transcription of the interferon-sensitive genes. The induced gene products then mediate the antiviral, immunomodulatory and other effects characteristically induced by interferons. 

Yet another strategy that may prove useful is the introduction into tumour cells of a sensitivity gene. This concept dictates that the gene product should harbour the ability to convert a non-toxic pro-drug into a toxic substance within the cells - thus leading to their selective destruction. The model system most used to appraise such an approach entails the use of the thymidine kinase gene of the herpes simplex virus (Figure 14.12). 

In most instances, ligand binding appears to promote receptor dimerization, bringing their associated JAKs into close proximity (Figure 4.2). The JAKs then phosphorylate — and hence activate — each other (transphosphorylation). The activated kinases subsequently phosphorylate specific tyrosine residues on the receptor itself. This promotes direct association between one or more members of a family of cytoplasmic proteins (STATs) and the receptor. Once docked at the receptor surface, the STATs are in turn phosphorylated (and hence activated) by the JAKs (Figure 4.2). As described below, activated STATs then translocate to the nucleus and directly regulate expression of IFN and other cytokine-sensitive genes. 

The three activated STATs disengage from the receptor and bind to the cytoplasmic protein, p48. This entire complex translocates to the nucleus, where it interacts directly with upstream regulatory regions of IFN-sensitive genes. These nucleotide sequences are termed interferon-stimulated response elements (ISREs). This induces/augments expression of specific genes, as discussed later. 

Zubay, G., D. Schwartz, and J. Beckwith, Mechanism of activation of catabolite-sensitive genes A positive control system. Proc. Natl. Acad. Sci. USA 66 104-110, 1970. First isolation of an activator protein. 

Roy S., Lado B. H., Khanna S., and Sen C. K. (2002). Vitamin E sensitive genes in the developing rat fetal brain a high-density oligonucleotide microarray analysis. FEBS Lett. 530 17-23. 

Multi-strain experiments common. Differences between strains often the starting point for identifying sensitivity genes... 

Fig. 4. Specificity determined by availability of receptor binding regions of DNA. With an oestrogen (E) sensitive gene, the receptor complex binds to specific regions of DNA (steroid response element) which influences the efficiency of mRNA initiation. If the response element is blocked, the gene is unresponsive to the steroid.

OXYGEN SENSING AND PREFERENTIAL 02-SENSITIVE GENE EXPRESSION... 

In overview, the hypoxia-sensitive expression of each of these kinds of proteins (EPO, PGK, and LDH), and of other glycolytic enzymes appears to be two-step or two-cycle systems (figure 3.14) the first cycles involve the constitutive expression of key hypoxia-sensitive transcription factors such as HIF 1 and Sp3, while the second cycles of gene expression are mediated by these transcription factors and regulate the biosynthesis of EPO, PGK, LDH, other glycolytic enzymes, and other hypoxia-sensitive gene products. 

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