Mechanical gene activation

The cis-acting elements that decrease or repress the expression of specific genes have also been identified. Because fewet of these elements have been smdied, it is not possible to fotmulate genetalizations about their mechanism of action—though again, as for gene activation, chromatin level covalent modifications of histones and other proteins by (repressor)-recruited multisubunit corepressors have been imphcated. 

In microbes without a permeability barrier, or when the barrier fails, a mechanism must be in place to export metals from the cytoplasm. These active transport systems involve energy-dependent, membrane-bound efflux pumps that can be encoded by either chromosomal- or plasmid-borne genes. Active transport is the most well-studied metal resistance mechanism. Some of these include the ars operon for exporting arsenic from E. coli, the cad system for exporting cadmium from Staphylococcus aureus, and the cop operon for removing excess copper from Enterococcus hiraeP i9A0... 

Mechanism of action Gene activation Second messenger systems Gene activation Second messenger systems... 

As with signal transduction and second messenger systems, the mechanism of gene activation allows for amplification of the hormone s effect. 

These findings complete the panorama relative to the mechanisms of hormonal action mediated by nuclear receptors. Thus, gene activation mediated by nuclear receptors can respond to three clearly differentiated modalities (1) receptor bound to hormone and not phosphorylated, (2) receptor bound to hormone and phosphorylated, and (3) receptor not bound to hormone and phosphorylated (Filardo 2002 Lee et al. 2002 Powles 2002). 

Casis, O., Olesen, S.P. and Sanguineth, M.C. (2006) Mechanism of action of a novel human ether-a-go-go-related gene activator. Molecular Pharmacology, 69, 658-665. 

Figure 21.6 One mechanism of activation of the cell cycle by a growth factor. Binding of growth factor to its receptor activates membrane-bound phospholipase-C. This hydrolyses phosphati-dylinositol bisphosphate in the membrane to produce the messengers, inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 results in release of Ca from an intracellular store. The increased Ca + ion concentration activates protein kinases including protein kinase-C (PK-C). DAG remains membrane-bound and also activates protein kinase-C (PK-C) which remains in the activated form as it travels through the cell where it phosphory-lates and activates transcription factors. This results in activation of genes that express enzymes involved in nucleotide synthesis, DNA polymerases and cyclins, which are all reguired for the cell cycle (See Chapter 20 for provision of nucleotides and cyclins for the cell cycle).

Wallberg, A.E., Neely, K.E., Hassan, A.H., Gustafsson, J.A., Workman, J.L., and Wright, A.P. (2000) Recruitment of the SWI-SNF chromatin remodeling complex as a mechanism of gene activation by the glucocorticoid receptor taul activation domain. Mol. Cell. Biol. 20, 2004-2013. 

Glass, C.K., Eu, X.D. and Roserrfeld, M.G. (2007) Histone mefhylation-dependent mechanisms impose ligand dependency for gene activation by nudear receptors. Cell, 128, 505-518. 

An imderstanding of the mechanism by which the highly specific and selective recognition of a nucleotide sequence is achieved is only possible with knowledge of the structural details of specific protein-nucleic acid complexes. For the regulation of gene activity the binding of proteins to double-stranded DNA is of central importance. We... 

The MAPK cascade in the plant s defense against bacterial pathogens is remarkably similar to the innate immune response triggered by bacterial lipopolysac-charide and mediated by the Toll-like receptors in mammals (Fig. 12-30b). Other membrane receptors use similar mechanisms to activate a MAPK cascade, ultimately activating transcription factors and turning on the genes essential to the defense response. 

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. 

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