Genes controllers

Transactivation. Protein synthesis is initiated or inhibited by the action of the activated GR on DNA. The use of glucocorticoids leads to antiinflammatory effects by first controlling gene expression, which subsequentiy leads to the synthesis and/or suppression of inflammation regulatory proteins. 

The ability of the leucine zipper proteins to form heterodimers greatly expands the repertoire of DNA-binding specificities that these proteins can display. As illustrated in Figure 10.19, for example, three distinct DNA-binding specificities could, in principle, be generated from two types of monomer, while six could be created from three types of monomer and so on. This is an example of combinatorial control, in which combinations of proteins, rather than individual proteins, control a cellular process. It is one of the most important mechanisms used by eucaryotic cells to control gene expression. 

Histone acetylation is a reversible and covalent modification of histone proteins introduced at the e-amino groups of lysine residues. Histones and DNA form a complex - chromatin - which condenses DNA and controls gene activity. Current models interpret histone acetylation as a means to regulate chromatin activity. 

Keaveney M, Struhl K Activator-mediated recruitment of the RNA polymerase machinery is the predominant mechanism for transcriptional activation in yeast. Mol Cell 1998 1 917. Lemon B, Tjian R Orchestrated response a symphony of transcription factors for gene control. Genes Dev 2000 l4 255l. Maniatis T, Reed R An extensive network of coupling among gene expression machines. Nature 2002 416 499. 

In addition to affecting the efficiency of promoter utilization, eukaryotic cells employ alternative RNA processing to control gene expression. This can result when alternative promoters, intron-exon splice sites, or polyadenylation sites are used. Occasionally, heterogeneity within a cell results, but more commonly the same primary transcript is processed differendy in different tissues. A few examples of each of these types of regulation are presented below. 

Lemon B, Tjian R Orchestrated response a symphony of transcription factors for gene control. Genes Dev 2000 14 2551. 

Booher, R., and Beach, D. (1986). Site-specific mutagenesis of cdc2+, a cell cycle control gene of the fission yeast Schizosaccaromyces pombe. Mol. Cell. Biol. 6 3523-3530. Booher, R. N., Alfa, C. E., Hyams, J. S., and Beach, D. H. (1989). The fission yeast cdc2/cdcl3/sucl protein kinase regulation of catalytic activity and nuclear localization. CeU 58 485-497. 

Enoch, T and Nurse, P. (1990). Mutation of the fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication. Cell 60 665-673. 

Gautier, J., Norbury, C., Lohka, M., Nurse, P., and Mailer, J. (1988). Purified maturation-promoting factor contains the product of a Xenopus homologue of the fission yeast cell cycle control gene cdc2+. Cell 54 433-439. 

Simanis, V., and Nurse, R (1986). The cell cycle control gene cdc2+ of fission yeast encodes a protein kinase potentially regulated by phosphorylation. Cell 45 261-268. 

TABLE 1 Major growth control genes in the mouse... 

Mierau, I. and Kleerebezem, M. (2005) 10 years of the nisin-controlled gene expression system (NICE) in Lactococcus lactis. Applied Microbiology and Biotechnology, 68 (6), 705—717. 

Beach, D., Durkacz, B. and Nurse, P. (1982) Functionally homologous cell cycle control genes in budding and fission yeast. Nature, 300 (5894), 706-709. 

Tomlinson, E., and Rolland, A.P., Controllable gene therapy pharmaceutics of nonviral gene delivery systems, Journal of Controlled Release, 1995, 39, 357-372. 

JAKs and signal transducers and activators of transcription (STATs) are functionally analogous with IRS and PI3K. JAKs are physically associated with a cell surface receptor (e.g. for leptin, erythropoietin (EPO), growth factors or cytokines) STATs are free monomeric proteins within the cytosol but following phosphorylation by a JAK, individual proteins dimerize and then move into the nucleus of the cell where they control gene expression. 

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