Human interferon gene

Gray PW, Goeddel DV. 1982. Structure of the human interferon gene. Nature. 298 859-863. 

Diaz MO, Bohlander S, Allen G (1993) Nomenclature of human interferon genes. J Interferon Res 13 234-243... 

Potentially, interferon is an ideal anhviral agent in that it acts on many different vimses and is not toxic to host cells. However, the exploitation of this agent in the treatment of viral infechons has been delayed by a number of factors. For example, it has proved to be species-specific and interferons raised in animal sources offered little protechon to human cells. Human interferon is thus needed for the treatment of human infechons and the produehon and purificahon of human interferon on a large scale has proved difficult. The inserhon of human genes for interferon into E. coli has resolved the produehon problems (Chapter 24). Clinical trials have demonstrated that interferon prevents rhinovirus infeehon and has a beneficial effect in herpes, cytomegalovims and hepahtis B vims infechons. 

Functional analysis of independently regulated transcription units the human type I interferon gene cluster as a paradigm... 

Expression of the human fibroblast interferon gene in Escherichia coli. Proc Natl Acad Sci USA, 1980. 77(9) 5230-3. 

Wilson, V., A.I. leffreys, P.A. Barrie, P.G. Boseley, P.M. Slocombe, A. Easton, and D.C. Burke, A comparison of vertebrate interferon gene families detected by hybridization with human interferon DNA. I Mol Biol, 1983.166(4) 457-75. 

Geng, Y., D. Yu, L.M. Blatt, and M.W. Taylor, Tumor suppressor activity of the human consensus type I interferon gene. Cytokines MolTher, 1995.1(4) 289-300. 

A. General description Interferon beta-la is produced by Chinese hamster ovary (CHO) cells into which the human interferon beta gene has been introduced. The amino-acid sequence of the recombinant protein produced by these cells is identical to naturally occurring interferon beta. Interferon beta-la is a single-chain glycosylated polypeptide, 166 amino-acid residues in length, with an approximate molecular weight of 22.5 kDa. 

Yoshida, J. et al. (2002). Antitumor effect of an adeno-associated virus vector containing the human interferon-beta gene on experimental intracranial human glioma. Jpn. J. Cancer Res. 93(2), 223-228. 

Klehr D, Maass K, Bode J (1991), Scaffold-attached regions from the human interferon beta domain can be used to enhance the stable expression of genes under the control of various promoters, Biochemistry 30 1264-1270. 

Mice and humans (and their respective cytokines and receptors) have been evolutionarily separated for over 100 million years. Consequently, the murine interferons differ from all of the human interferons at fifty-six to seventy-two amino-acid positions. Nevertheless, it was possible, simply by recombining human sequences, to produce an interferon with an activity greater than that of the natural mouse protein. Sequences that had been pre-tested in humans to function as a-interferons contained the information necessary to build a protein that functions well with murine cells. Even though it was not possible to reconstruct the exact sequence of murine a-interferon from the human genes, it was possible to reconstruct its function. 

Binding of human interferon-lb to specific cell receptors induces the expression of a number of interferon-induced gene products (e.g., 2, 5 -oligoandenylate synthetase, protein kinase, and indoleamine 2,3-dioxygenase that are believed to be mediators of the biological actions... 

Derynck, R., Content,J., DeClercq, E., Volckaert, G., Tavernier,J., Devos, R., and Fiers, W. (1980). Isolation and structure of a human fibroblast interferon gene. Nature 285, 542-547. 

Fig. 4. Sequence comparison of IL-6, IFN-y, CNTF-responsive elements. Modified from Caldenhoven et al. (1994) and Bonni et al. (1993). Abbreviations rat a2M, the rat al macroglobulin hICAM-I, human ICAM-I hIRF-1, human interferon regulatory factor-1 hGBP, human GBP gene CNTF-RE, CNTF-responsive elements and IFN-y-activated site are also shown (Darnell et al., 1994).

P450 8A1 is constitutively expressed in human endothelial cells . The human CYP8A1 gene (chromosome 20) has 10 exons and has consensus sequences for Spl, AP-2, an interferon--/ response element, GATA NF, B, a CACCC box, glucocorticoid receptor, and a shear stress responsive element (GAGACC) . Whether or not all of these are functional and how they interact to maintain constitutive expression is not well understood yet. 

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